diff --git a/Lib/re.py b/Lib/re.py
index 8f5b399..e731a69 100644
--- a/Lib/re.py
+++ b/Lib/re.py
@@ -122,6 +122,7 @@
 import sys
 import sre_compile
 import sre_parse
+import _locale
 
 # public symbols
 __all__ = [
@@ -274,7 +275,9 @@
 def _compile(pattern, flags):
     # internal: compile pattern
     try:
-        return _cache[type(pattern), pattern, flags]
+        p, loc = _cache[type(pattern), pattern, flags]
+        if loc is None or loc == _locale.setlocale(_locale.LC_CTYPE):
+            return p
     except KeyError:
         pass
     if isinstance(pattern, _pattern_type):
@@ -288,7 +291,11 @@
     if not (flags & DEBUG):
         if len(_cache) >= _MAXCACHE:
             _cache.clear()
-        _cache[type(pattern), pattern, flags] = p
+        if p.flags & LOCALE:
+            loc = _locale.setlocale(_locale.LC_CTYPE)
+        else:
+            loc = None
+        _cache[type(pattern), pattern, flags] = p, loc
     return p
 
 def _compile_repl(repl, pattern):
diff --git a/Lib/test/test_re.py b/Lib/test/test_re.py
index dfc797c..4029561 100644
--- a/Lib/test/test_re.py
+++ b/Lib/test/test_re.py
@@ -1,6 +1,7 @@
 from test.support import verbose, run_unittest, gc_collect, bigmemtest, _2G, \
         cpython_only, captured_stdout
 import io
+import locale
 import re
 from re import Scanner
 import sre_compile
@@ -1276,6 +1277,42 @@
         # with ignore case.
         self.assertEqual(re.fullmatch('[a-c]+', 'ABC', re.I).span(), (0, 3))
 
+    def test_locale_caching(self):
+        # Issue #22410
+        oldlocale = locale.setlocale(locale.LC_CTYPE)
+        self.addCleanup(locale.setlocale, locale.LC_CTYPE, oldlocale)
+        for loc in 'en_US.iso88591', 'en_US.utf8':
+            try:
+                locale.setlocale(locale.LC_CTYPE, loc)
+            except locale.Error:
+                # Unsupported locale on this system
+                self.skipTest('test needs %s locale' % loc)
+
+        re.purge()
+        self.check_en_US_iso88591()
+        self.check_en_US_utf8()
+        re.purge()
+        self.check_en_US_utf8()
+        self.check_en_US_iso88591()
+
+    def check_en_US_iso88591(self):
+        locale.setlocale(locale.LC_CTYPE, 'en_US.iso88591')
+        self.assertTrue(re.match(b'\xc5\xe5', b'\xc5\xe5', re.L|re.I))
+        self.assertTrue(re.match(b'\xc5', b'\xe5', re.L|re.I))
+        self.assertTrue(re.match(b'\xe5', b'\xc5', re.L|re.I))
+        self.assertTrue(re.match(b'(?Li)\xc5\xe5', b'\xc5\xe5'))
+        self.assertTrue(re.match(b'(?Li)\xc5', b'\xe5'))
+        self.assertTrue(re.match(b'(?Li)\xe5', b'\xc5'))
+
+    def check_en_US_utf8(self):
+        locale.setlocale(locale.LC_CTYPE, 'en_US.utf8')
+        self.assertTrue(re.match(b'\xc5\xe5', b'\xc5\xe5', re.L|re.I))
+        self.assertIsNone(re.match(b'\xc5', b'\xe5', re.L|re.I))
+        self.assertIsNone(re.match(b'\xe5', b'\xc5', re.L|re.I))
+        self.assertTrue(re.match(b'(?Li)\xc5\xe5', b'\xc5\xe5'))
+        self.assertIsNone(re.match(b'(?Li)\xc5', b'\xe5'))
+        self.assertIsNone(re.match(b'(?Li)\xe5', b'\xc5'))
+
 
 class PatternReprTests(unittest.TestCase):
     def check(self, pattern, expected):
diff --git a/Misc/NEWS b/Misc/NEWS
index 76fdd8d..dd2aeb6 100644
--- a/Misc/NEWS
+++ b/Misc/NEWS
@@ -180,6 +180,9 @@
 Library
 -------
 
+- Issue #22410: Module level functions in the re module now cache compiled
+  locale-dependent regular expressions taking into account the locale.
+
 - Issue #22759: Query methods on pathlib.Path() (exists(), is_dir(), etc.)
   now return False when the underlying stat call raises NotADirectoryError.