diff --git a/doc/source/whatsnew/v1.3.0.rst b/doc/source/whatsnew/v1.3.0.rst
index 74710ca48308c..441116376d52b 100644
--- a/doc/source/whatsnew/v1.3.0.rst
+++ b/doc/source/whatsnew/v1.3.0.rst
@@ -913,6 +913,7 @@ Other
 - Bug in :func:`pandas.testing.assert_series_equal`, :func:`pandas.testing.assert_frame_equal`, :func:`pandas.testing.assert_index_equal` and :func:`pandas.testing.assert_extension_array_equal` incorrectly raising when an attribute has an unrecognized NA type (:issue:`39461`)
 - Bug in :meth:`DataFrame.equals`, :meth:`Series.equals`, :meth:`Index.equals` with object-dtype containing ``np.datetime64("NaT")`` or ``np.timedelta64("NaT")`` (:issue:`39650`)
 - Bug in :func:`pandas.util.show_versions` where console JSON output was not proper JSON (:issue:`39701`)
+- Let Pandas compile on z/OS when using `xlc <https://www.ibm.com/products/xl-cpp-compiler-zos>`_ (:issue:`35826`)
 - Bug in :meth:`DataFrame.convert_dtypes` incorrectly raised ValueError when called on an empty DataFrame (:issue:`40393`)
 - Bug in :meth:`DataFrame.clip` not interpreting missing values as no threshold (:issue:`40420`)
 
diff --git a/pandas/_libs/src/headers/cmath b/pandas/_libs/src/headers/cmath
index 632e1fc2390d0..9e7540cfefc13 100644
--- a/pandas/_libs/src/headers/cmath
+++ b/pandas/_libs/src/headers/cmath
@@ -25,6 +25,18 @@ namespace std {
   __inline int isnan(double x) { return _isnan(x); }
   __inline int notnan(double x) { return x == x; }
 }
+#elif defined(__MVS__)
+#include <cmath>
+
+#define _signbit signbit
+#undef signbit
+#undef isnan
+
+namespace std {
+  __inline int notnan(double x) { return x == x; }
+  __inline int signbit(double num) { return _signbit(num); }
+  __inline int isnan(double x) { return isnan(x); }
+}
 #else
 #include <cmath>
 
diff --git a/setup.py b/setup.py
index b410c5c154648..17ee110bc4136 100755
--- a/setup.py
+++ b/setup.py
@@ -569,6 +569,17 @@ def srcpath(name=None, suffix=".pyx", subdir="src"):
     include = data.get("include", [])
     include.append(numpy.get_include())
 
+    undef_macros = []
+
+    if (
+        sys.platform == "zos"
+        and data.get("language") == "c++"
+        and os.path.basename(os.environ.get("CXX", "/bin/xlc++")) in ("xlc", "xlc++")
+    ):
+        data.get("macros", macros).append(("__s390__", "1"))
+        extra_compile_args.append("-qlanglvl=extended0x:nolibext")
+        undef_macros.append("_POSIX_THREADS")
+
     obj = Extension(
         f"pandas.{name}",
         sources=sources,
@@ -578,6 +589,7 @@ def srcpath(name=None, suffix=".pyx", subdir="src"):
         define_macros=data.get("macros", macros),
         extra_compile_args=extra_compile_args,
         extra_link_args=extra_link_args,
+        undef_macros=undef_macros,
     )
 
     extensions.append(obj)