diff --git a/Doc/whatsnew/3.11.rst b/Doc/whatsnew/3.11.rst
index 8db26cd0126b3a..3c834d0ac47d54 100644
--- a/Doc/whatsnew/3.11.rst
+++ b/Doc/whatsnew/3.11.rst
@@ -675,6 +675,39 @@ Porting to Python 3.11
   been included directly, consider including ``Python.h`` instead.
   (Contributed by Victor Stinner in :issue:`35134`.)
 
+* The following "GET" and "AS" functions can no longer be used as l-value (to
+  modify a Python object):
+
+  * :c:func:`PyByteArray_GET_SIZE`
+  * :c:func:`PyBytes_GET_SIZE`
+  * :c:func:`PyCFunction_GET_CLASS`
+  * :c:func:`PyCFunction_GET_FLAGS`
+  * :c:func:`PyCFunction_GET_FUNCTION`
+  * :c:func:`PyCFunction_GET_SELF`
+  * :c:func:`PyDict_GET_SIZE`
+  * :c:func:`PyFloat_AS_DOUBLE`
+  * :c:func:`PyFunction_GET_ANNOTATIONS`
+  * :c:func:`PyFunction_GET_CLOSURE`
+  * :c:func:`PyFunction_GET_CODE`
+  * :c:func:`PyFunction_GET_DEFAULTS`
+  * :c:func:`PyFunction_GET_GLOBALS`
+  * :c:func:`PyFunction_GET_KW_DEFAULTS`
+  * :c:func:`PyFunction_GET_MODULE`
+  * :c:func:`PyHeapType_GET_MEMBERS`
+  * :c:func:`PyInstanceMethod_GET_FUNCTION`
+  * :c:func:`PyList_GET_SIZE`
+  * :c:func:`PyMemoryView_GET_BASE`
+  * :c:func:`PyMemoryView_GET_BUFFER`
+  * :c:func:`PyMethod_GET_FUNCTION`
+  * :c:func:`PyMethod_GET_SELF`
+  * :c:func:`PySet_GET_SIZE`
+  * :c:func:`PyTuple_GET_SIZE`
+  * :c:func:`PyWeakref_GET_OBJECT`
+
+  For example, ``PyList_GET_SIZE(list) = 5;`` now fails with a compiler error.
+  The :c:func:`Py_SET_SIZE` function must be used instead.
+  (Contributed by Victor Stinner in :issue:`45476`.)
+
 Deprecated
 ----------
 
diff --git a/Include/cpython/bytearrayobject.h b/Include/cpython/bytearrayobject.h
index 569b0cd0369861..34cfb253738b27 100644
--- a/Include/cpython/bytearrayobject.h
+++ b/Include/cpython/bytearrayobject.h
@@ -11,10 +11,13 @@ typedef struct {
     Py_ssize_t ob_exports; /* How many buffer exports */
 } PyByteArrayObject;
 
+PyAPI_DATA(char) _PyByteArray_empty_string[];
+
 /* Macros, trading safety for speed */
+#define _PyByteArray_CAST(op) \
+    (assert(PyByteArray_Check(op)), (PyByteArrayObject *)(op))
 #define PyByteArray_AS_STRING(self) \
     (assert(PyByteArray_Check(self)), \
      Py_SIZE(self) ? ((PyByteArrayObject *)(self))->ob_start : _PyByteArray_empty_string)
-#define PyByteArray_GET_SIZE(self) (assert(PyByteArray_Check(self)), Py_SIZE(self))
-
-PyAPI_DATA(char) _PyByteArray_empty_string[];
+#define PyByteArray_GET_SIZE(self) \
+    _Py_RVALUE(Py_SIZE(_PyByteArray_CAST(self)))
diff --git a/Include/cpython/bytesobject.h b/Include/cpython/bytesobject.h
index 6b3f55224fc553..eb6129a65b3aa3 100644
--- a/Include/cpython/bytesobject.h
+++ b/Include/cpython/bytesobject.h
@@ -29,9 +29,9 @@ PyAPI_FUNC(PyObject *) _PyBytes_DecodeEscape(const char *, Py_ssize_t,
                                              const char *, const char **);
 
 /* Macro, trading safety for speed */
-#define PyBytes_AS_STRING(op) (assert(PyBytes_Check(op)), \
-                                (((PyBytesObject *)(op))->ob_sval))
-#define PyBytes_GET_SIZE(op)  (assert(PyBytes_Check(op)),Py_SIZE(op))
+#define _PyBytes_CAST(op) (assert(PyBytes_Check(op)), (PyBytesObject *)(op))
+#define PyBytes_AS_STRING(op) (_PyBytes_CAST(op)->ob_sval)
+#define PyBytes_GET_SIZE(op) _Py_RVALUE(Py_SIZE(_PyBytes_CAST(op)))
 
 /* _PyBytes_Join(sep, x) is like sep.join(x).  sep must be PyBytesObject*,
    x must be an iterable object. */
diff --git a/Include/cpython/classobject.h b/Include/cpython/classobject.h
index 80df8842eb4f78..51d0233e704ee5 100644
--- a/Include/cpython/classobject.h
+++ b/Include/cpython/classobject.h
@@ -29,9 +29,9 @@ PyAPI_FUNC(PyObject *) PyMethod_Self(PyObject *);
 /* Macros for direct access to these values. Type checks are *not*
    done, so use with care. */
 #define PyMethod_GET_FUNCTION(meth) \
-        (((PyMethodObject *)meth) -> im_func)
+        _Py_RVALUE(((PyMethodObject *)meth) -> im_func)
 #define PyMethod_GET_SELF(meth) \
-        (((PyMethodObject *)meth) -> im_self)
+        _Py_RVALUE(((PyMethodObject *)meth) -> im_self)
 
 typedef struct {
     PyObject_HEAD
@@ -48,7 +48,7 @@ PyAPI_FUNC(PyObject *) PyInstanceMethod_Function(PyObject *);
 /* Macros for direct access to these values. Type checks are *not*
    done, so use with care. */
 #define PyInstanceMethod_GET_FUNCTION(meth) \
-        (((PyInstanceMethodObject *)meth) -> func)
+        _Py_RVALUE(((PyInstanceMethodObject *)meth) -> func)
 
 #ifdef __cplusplus
 }
diff --git a/Include/cpython/dictobject.h b/Include/cpython/dictobject.h
index e97969be4de0cc..cbf1e655944c28 100644
--- a/Include/cpython/dictobject.h
+++ b/Include/cpython/dictobject.h
@@ -46,7 +46,8 @@ PyAPI_FUNC(int) _PyDict_Next(
     PyObject *mp, Py_ssize_t *pos, PyObject **key, PyObject **value, Py_hash_t *hash);
 
 /* Get the number of items of a dictionary. */
-#define PyDict_GET_SIZE(mp)  (assert(PyDict_Check(mp)),((PyDictObject *)mp)->ma_used)
+#define PyDict_GET_SIZE(mp) \
+    _Py_RVALUE((assert(PyDict_Check(mp)), ((PyDictObject *)mp)->ma_used))
 PyAPI_FUNC(int) _PyDict_Contains_KnownHash(PyObject *, PyObject *, Py_hash_t);
 PyAPI_FUNC(int) _PyDict_ContainsId(PyObject *, struct _Py_Identifier *);
 PyAPI_FUNC(PyObject *) _PyDict_NewPresized(Py_ssize_t minused);
diff --git a/Include/cpython/floatobject.h b/Include/cpython/floatobject.h
index fffd468690274e..c9c132651dd05a 100644
--- a/Include/cpython/floatobject.h
+++ b/Include/cpython/floatobject.h
@@ -8,5 +8,6 @@ typedef struct {
 } PyFloatObject;
 
 // Macro version of PyFloat_AsDouble() trading safety for speed.
-// It doesn't check if op is a double object.
-#define PyFloat_AS_DOUBLE(op) (((PyFloatObject *)(op))->ob_fval)
+// It only checks if op is a double object in debug mode.
+#define _PyFloat_CAST(op) (assert(PyFloat_Check(op)), (PyFloatObject *)(op))
+#define PyFloat_AS_DOUBLE(op) _Py_RVALUE(_PyFloat_CAST(op)->ob_fval)
diff --git a/Include/cpython/funcobject.h b/Include/cpython/funcobject.h
index 9f0560fb725036..27d9a7c8fbdc40 100644
--- a/Include/cpython/funcobject.h
+++ b/Include/cpython/funcobject.h
@@ -86,20 +86,21 @@ uint32_t _PyFunction_GetVersionForCurrentState(PyFunctionObject *func);
 
 /* Macros for direct access to these values. Type checks are *not*
    done, so use with care. */
+#define _PyFunction_CAST(func) ((PyFunctionObject *)func)
 #define PyFunction_GET_CODE(func) \
-        (((PyFunctionObject *)func) -> func_code)
+        _Py_RVALUE(_PyFunction_CAST(func)->func_code)
 #define PyFunction_GET_GLOBALS(func) \
-        (((PyFunctionObject *)func) -> func_globals)
+        _Py_RVALUE(_PyFunction_CAST(func)->func_globals)
 #define PyFunction_GET_MODULE(func) \
-        (((PyFunctionObject *)func) -> func_module)
+        _Py_RVALUE(_PyFunction_CAST(func)->func_module)
 #define PyFunction_GET_DEFAULTS(func) \
-        (((PyFunctionObject *)func) -> func_defaults)
+        _Py_RVALUE(_PyFunction_CAST(func)->func_defaults)
 #define PyFunction_GET_KW_DEFAULTS(func) \
-        (((PyFunctionObject *)func) -> func_kwdefaults)
+        _Py_RVALUE(_PyFunction_CAST(func)->func_kwdefaults)
 #define PyFunction_GET_CLOSURE(func) \
-        (((PyFunctionObject *)func) -> func_closure)
+        _Py_RVALUE(_PyFunction_CAST(func)->func_closure)
 #define PyFunction_GET_ANNOTATIONS(func) \
-        (((PyFunctionObject *)func) -> func_annotations)
+        _Py_RVALUE(_PyFunction_CAST(func)->func_annotations)
 
 /* The classmethod and staticmethod types lives here, too */
 PyAPI_DATA(PyTypeObject) PyClassMethod_Type;
diff --git a/Include/cpython/listobject.h b/Include/cpython/listobject.h
index 51687d866ce971..c596fa500a6ba4 100644
--- a/Include/cpython/listobject.h
+++ b/Include/cpython/listobject.h
@@ -31,4 +31,4 @@ PyAPI_FUNC(void) _PyList_DebugMallocStats(FILE *out);
 
 #define PyList_GET_ITEM(op, i) (_PyList_CAST(op)->ob_item[i])
 #define PyList_SET_ITEM(op, i, v) _Py_RVALUE(_PyList_CAST(op)->ob_item[i] = (v))
-#define PyList_GET_SIZE(op)    Py_SIZE(_PyList_CAST(op))
+#define PyList_GET_SIZE(op) _Py_RVALUE(Py_SIZE(_PyList_CAST(op)))
diff --git a/Include/cpython/methodobject.h b/Include/cpython/methodobject.h
index 7ecbfe3b5e2fe8..3361cbdd238952 100644
--- a/Include/cpython/methodobject.h
+++ b/Include/cpython/methodobject.h
@@ -9,16 +9,18 @@ PyAPI_DATA(PyTypeObject) PyCMethod_Type;
 
 /* Macros for direct access to these values. Type checks are *not*
    done, so use with care. */
+#define _PyCFunction_CAST(func) ((PyCFunctionObject *)func)
+#define _PyCFunction_ML(func) (_PyCFunction_CAST(func)->m_ml)
 #define PyCFunction_GET_FUNCTION(func) \
-        (((PyCFunctionObject *)func) -> m_ml -> ml_meth)
+        _Py_RVALUE(_PyCFunction_ML(func)->ml_meth)
 #define PyCFunction_GET_SELF(func) \
-        (((PyCFunctionObject *)func) -> m_ml -> ml_flags & METH_STATIC ? \
-         NULL : ((PyCFunctionObject *)func) -> m_self)
+        _Py_RVALUE(_PyCFunction_ML(func)->ml_flags & METH_STATIC ? \
+                   NULL : _PyCFunction_CAST(func)->m_self)
 #define PyCFunction_GET_FLAGS(func) \
-        (((PyCFunctionObject *)func) -> m_ml -> ml_flags)
+        _Py_RVALUE(_PyCFunction_ML(func)-> ml_flags)
 #define PyCFunction_GET_CLASS(func) \
-    (((PyCFunctionObject *)func) -> m_ml -> ml_flags & METH_METHOD ? \
-         ((PyCMethodObject *)func) -> mm_class : NULL)
+        _Py_RVALUE(_PyCFunction_ML(func)->ml_flags & METH_METHOD ? \
+                   ((PyCMethodObject *)func)->mm_class : NULL)
 
 typedef struct {
     PyObject_HEAD
diff --git a/Include/cpython/object.h b/Include/cpython/object.h
index 3a8a256e3b9ae6..c28f2fd90c61ad 100644
--- a/Include/cpython/object.h
+++ b/Include/cpython/object.h
@@ -296,7 +296,7 @@ typedef struct _heaptypeobject {
 
 /* access macro to the members which are floating "behind" the object */
 #define PyHeapType_GET_MEMBERS(etype) \
-    ((PyMemberDef *)(((char *)etype) + Py_TYPE(etype)->tp_basicsize))
+    _Py_RVALUE((PyMemberDef *)(((char *)etype) + Py_TYPE(etype)->tp_basicsize))
 
 PyAPI_FUNC(const char *) _PyType_Name(PyTypeObject *);
 PyAPI_FUNC(PyObject *) _PyType_Lookup(PyTypeObject *, PyObject *);
diff --git a/Include/cpython/tupleobject.h b/Include/cpython/tupleobject.h
index fc37c4e6de1cab..56ec8812a32400 100644
--- a/Include/cpython/tupleobject.h
+++ b/Include/cpython/tupleobject.h
@@ -18,8 +18,11 @@ PyAPI_FUNC(void) _PyTuple_MaybeUntrack(PyObject *);
 /* Cast argument to PyTupleObject* type. */
 #define _PyTuple_CAST(op) (assert(PyTuple_Check(op)), (PyTupleObject *)(op))
 
-#define PyTuple_GET_SIZE(op)    Py_SIZE(_PyTuple_CAST(op))
+#define PyTuple_GET_SIZE(op) _Py_RVALUE(Py_SIZE(_PyTuple_CAST(op)))
 
+// Don't use _Py_RVALUE() for now since many C extensions abuse
+// PyTuple_GET_ITEM() to get the PyTuple_GET_ITEM.ob_item array
+// using: "&PyTuple_GET_ITEM(tuple, 0)".
 #define PyTuple_GET_ITEM(op, i) (_PyTuple_CAST(op)->ob_item[i])
 
 /* Macro, *only* to be used to fill in brand new tuples */
diff --git a/Include/cpython/weakrefobject.h b/Include/cpython/weakrefobject.h
index 9efcc412df9bed..231dc12ae89d13 100644
--- a/Include/cpython/weakrefobject.h
+++ b/Include/cpython/weakrefobject.h
@@ -41,7 +41,7 @@ PyAPI_FUNC(void) _PyWeakref_ClearRef(PyWeakReference *self);
    has dropped to zero.  In the meantime, code accessing the weakref will
    be able to "see" the target object even though it is supposed to be
    unreachable.  See issue #16602. */
-#define PyWeakref_GET_OBJECT(ref)                           \
-    (Py_REFCNT(((PyWeakReference *)(ref))->wr_object) > 0   \
-     ? ((PyWeakReference *)(ref))->wr_object                \
-     : Py_None)
+#define PyWeakref_GET_OBJECT(ref) \
+    _Py_RVALUE(Py_REFCNT(((PyWeakReference *)(ref))->wr_object) > 0 \
+               ? ((PyWeakReference *)(ref))->wr_object \
+               : Py_None)
diff --git a/Include/memoryobject.h b/Include/memoryobject.h
index 306028f4b225d8..a12d5d56878063 100644
--- a/Include/memoryobject.h
+++ b/Include/memoryobject.h
@@ -15,9 +15,11 @@ PyAPI_DATA(PyTypeObject) PyMemoryView_Type;
 
 #ifndef Py_LIMITED_API
 /* Get a pointer to the memoryview's private copy of the exporter's buffer. */
-#define PyMemoryView_GET_BUFFER(op) (&((PyMemoryViewObject *)(op))->view)
+#define PyMemoryView_GET_BUFFER(op) \
+    _Py_RVALUE(&((PyMemoryViewObject *)(op))->view)
 /* Get a pointer to the exporting object (this may be NULL!). */
-#define PyMemoryView_GET_BASE(op) (((PyMemoryViewObject *)(op))->view.obj)
+#define PyMemoryView_GET_BASE(op) \
+    _Py_RVALUE(((PyMemoryViewObject *)(op))->view.obj)
 #endif
 
 PyAPI_FUNC(PyObject *) PyMemoryView_FromObject(PyObject *base);
diff --git a/Include/setobject.h b/Include/setobject.h
index 62516be5ab29be..9db68d5dbdabe3 100644
--- a/Include/setobject.h
+++ b/Include/setobject.h
@@ -64,7 +64,8 @@ typedef struct {
     PyObject *weakreflist;      /* List of weak references */
 } PySetObject;
 
-#define PySet_GET_SIZE(so) (assert(PyAnySet_Check(so)),(((PySetObject *)(so))->used))
+#define PySet_GET_SIZE(so) \
+    _Py_RVALUE((assert(PyAnySet_Check(so)), ((PySetObject *)(so))->used))
 
 PyAPI_DATA(PyObject *) _PySet_Dummy;
 
diff --git a/Misc/NEWS.d/next/C API/2021-11-30-11-12-53.bpo-45476.IFVjjP.rst b/Misc/NEWS.d/next/C API/2021-11-30-11-12-53.bpo-45476.IFVjjP.rst
new file mode 100644
index 00000000000000..1f0f2c8fb19c9f
--- /dev/null
+++ b/Misc/NEWS.d/next/C API/2021-11-30-11-12-53.bpo-45476.IFVjjP.rst	
@@ -0,0 +1,33 @@
+The following "GET" and "AS" functions can no longer be used as l-value (to
+modify a Python object):
+
+* :c:func:`PyByteArray_GET_SIZE`
+* :c:func:`PyBytes_GET_SIZE`
+* :c:func:`PyCFunction_GET_CLASS`
+* :c:func:`PyCFunction_GET_FLAGS`
+* :c:func:`PyCFunction_GET_FUNCTION`
+* :c:func:`PyCFunction_GET_SELF`
+* :c:func:`PyDict_GET_SIZE`
+* :c:func:`PyFloat_AS_DOUBLE`
+* :c:func:`PyFunction_GET_ANNOTATIONS`
+* :c:func:`PyFunction_GET_CLOSURE`
+* :c:func:`PyFunction_GET_CODE`
+* :c:func:`PyFunction_GET_DEFAULTS`
+* :c:func:`PyFunction_GET_GLOBALS`
+* :c:func:`PyFunction_GET_KW_DEFAULTS`
+* :c:func:`PyFunction_GET_MODULE`
+* :c:func:`PyHeapType_GET_MEMBERS`
+* :c:func:`PyInstanceMethod_GET_FUNCTION`
+* :c:func:`PyList_GET_SIZE`
+* :c:func:`PyMemoryView_GET_BASE`
+* :c:func:`PyMemoryView_GET_BUFFER`
+* :c:func:`PyMethod_GET_FUNCTION`
+* :c:func:`PyMethod_GET_SELF`
+* :c:func:`PySet_GET_SIZE`
+* :c:func:`PyTuple_GET_SIZE`
+* :c:func:`PyWeakref_GET_OBJECT`
+
+For example, ``PyList_GET_SIZE(list) = 5;`` now fails with a compiler error.
+The :c:func:`Py_SET_SIZE` function must be used instead.
+
+Patch by Victor Stinner.