diff --git a/CHANGELOG.md b/CHANGELOG.md
index cf3013e82d..7a2d5be115 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -37,6 +37,7 @@ We use _breaking :warning:_ to mark changes that are not backward compatible (re
 - [#3560](https://github.com/thanos-io/thanos/pull/3560) query-frontend: Allow separate label cache
 - [#3672](https://github.com/thanos-io/thanos/pull/3672) rule: prevent rule crash from no such host error when using `dnssrv+` or `dnssrvnoa+`.
 - [#3760](https://github.com/thanos-io/thanos/pull/3760) Store: Fix panic caused by a race condition happening on concurrent index-header reader usage and unload, when `--store.enable-index-header-lazy-reader` is enabled.
+- [#3759](https://github.com/thanos-io/thanos/pull/3759) Store: Fix panic caused by a race condition happening on concurrent index-header lazy load and unload, when `--store.enable-index-header-lazy-reader` is enabled.
 
 ### Changed
 
diff --git a/pkg/block/indexheader/lazy_binary_reader.go b/pkg/block/indexheader/lazy_binary_reader.go
index 0598e46f49..d4b9dee03b 100644
--- a/pkg/block/indexheader/lazy_binary_reader.go
+++ b/pkg/block/indexheader/lazy_binary_reader.go
@@ -24,7 +24,8 @@ import (
 )
 
 var (
-	errNotIdle = errors.New("the reader is not idle")
+	errNotIdle              = errors.New("the reader is not idle")
+	errUnloadedWhileLoading = errors.New("the index-header has been concurrently unloaded")
 )
 
 // LazyBinaryReaderMetrics holds metrics tracked by LazyBinaryReader.
@@ -208,7 +209,7 @@ func (r *LazyBinaryReader) LabelNames() ([]string, error) {
 
 // load ensures the underlying binary index-header reader has been successfully loaded. Returns
 // an error on failure. This function MUST be called with the read lock already acquired.
-func (r *LazyBinaryReader) load() error {
+func (r *LazyBinaryReader) load() (returnErr error) {
 	// Nothing to do if we already tried loading it.
 	if r.reader != nil {
 		return nil
@@ -221,8 +222,16 @@ func (r *LazyBinaryReader) load() error {
 	// the read lock once done.
 	r.readerMx.RUnlock()
 	r.readerMx.Lock()
-	defer r.readerMx.RLock()
-	defer r.readerMx.Unlock()
+	defer func() {
+		r.readerMx.Unlock()
+		r.readerMx.RLock()
+
+		// Between the write unlock and the subsequent read lock, the unload() may have run,
+		// so we make sure to catch this edge case.
+		if returnErr == nil && r.reader == nil {
+			returnErr = errUnloadedWhileLoading
+		}
+	}()
 
 	// Ensure none else tried to load it in the meanwhile.
 	if r.reader != nil {
diff --git a/pkg/block/indexheader/lazy_binary_reader_test.go b/pkg/block/indexheader/lazy_binary_reader_test.go
index 0b130199b6..886c0516fe 100644
--- a/pkg/block/indexheader/lazy_binary_reader_test.go
+++ b/pkg/block/indexheader/lazy_binary_reader_test.go
@@ -8,6 +8,7 @@ import (
 	"io/ioutil"
 	"os"
 	"path/filepath"
+	"sync"
 	"testing"
 	"time"
 
@@ -217,3 +218,71 @@ func TestLazyBinaryReader_unload_ShouldReturnErrorIfNotIdle(t *testing.T) {
 	testutil.Equals(t, float64(1), promtestutil.ToFloat64(m.unloadCount))
 	testutil.Equals(t, float64(0), promtestutil.ToFloat64(m.unloadFailedCount))
 }
+
+func TestLazyBinaryReader_LoadUnloadRaceCondition(t *testing.T) {
+	// Run the test for a fixed amount of time.
+	const runDuration = 5 * time.Second
+
+	ctx := context.Background()
+
+	tmpDir, err := ioutil.TempDir("", "test-indexheader")
+	testutil.Ok(t, err)
+	defer func() { testutil.Ok(t, os.RemoveAll(tmpDir)) }()
+
+	bkt, err := filesystem.NewBucket(filepath.Join(tmpDir, "bkt"))
+	testutil.Ok(t, err)
+	defer func() { testutil.Ok(t, bkt.Close()) }()
+
+	// Create block.
+	blockID, err := e2eutil.CreateBlock(ctx, tmpDir, []labels.Labels{
+		{{Name: "a", Value: "1"}},
+		{{Name: "a", Value: "2"}},
+	}, 100, 0, 1000, labels.Labels{{Name: "ext1", Value: "1"}}, 124)
+	testutil.Ok(t, err)
+	testutil.Ok(t, block.Upload(ctx, log.NewNopLogger(), bkt, filepath.Join(tmpDir, blockID.String())))
+
+	m := NewLazyBinaryReaderMetrics(nil)
+	r, err := NewLazyBinaryReader(ctx, log.NewNopLogger(), bkt, tmpDir, blockID, 3, m, nil)
+	testutil.Ok(t, err)
+	testutil.Assert(t, r.reader == nil)
+	t.Cleanup(func() {
+		testutil.Ok(t, r.Close())
+	})
+
+	done := make(chan struct{})
+	time.AfterFunc(runDuration, func() { close(done) })
+	wg := sync.WaitGroup{}
+	wg.Add(2)
+
+	// Start a goroutine which continuously try to unload the reader.
+	go func() {
+		defer wg.Done()
+
+		for {
+			select {
+			case <-done:
+				return
+			default:
+				testutil.Ok(t, r.unloadIfIdleSince(0))
+			}
+		}
+	}()
+
+	// Try to read multiple times, while the other goroutine continuously try to unload it.
+	go func() {
+		defer wg.Done()
+
+		for {
+			select {
+			case <-done:
+				return
+			default:
+				_, err := r.PostingsOffset("a", "1")
+				testutil.Assert(t, err == nil || err == errUnloadedWhileLoading)
+			}
+		}
+	}()
+
+	// Wait until both goroutines have done.
+	wg.Wait()
+}