diff --git a/CHANGES/6181.bugfix b/CHANGES/6181.bugfix
new file mode 100644
index 00000000000..70696784fa7
--- /dev/null
+++ b/CHANGES/6181.bugfix
@@ -0,0 +1 @@
+Make JSON media type matching case insensitive per RFC 2045.
diff --git a/aiohttp/helpers.py b/aiohttp/helpers.py
index 3cb94fd8902..92c0700ac06 100644
--- a/aiohttp/helpers.py
+++ b/aiohttp/helpers.py
@@ -124,7 +124,7 @@ def iscoroutinefunction(func: Any) -> bool:
         return asyncio.iscoroutinefunction(func)
 
 
-json_re = re.compile(r"(?:application/|[\w.-]+/[\w.+-]+?\+)json")
+json_re = re.compile(r"(?:application/|[\w.-]+/[\w.+-]+?\+)json", re.IGNORECASE)
 
 
 class BasicAuth(namedtuple("BasicAuth", ["login", "password", "encoding"])):
diff --git a/tests/test_helpers.py b/tests/test_helpers.py
index dae39015b9a..33c1d292545 100644
--- a/tests/test_helpers.py
+++ b/tests/test_helpers.py
@@ -747,6 +747,15 @@ def test_is_expected_content_type_non_application_json_private_suffix():
     )
 
 
+def test_is_expected_content_type_json_non_lowercase():
+    """Per RFC 2045, media type matching is case insensitive."""
+    expected_ct = "application/json"
+    response_ct = "Application/JSON"
+    assert is_expected_content_type(
+        response_content_type=response_ct, expected_content_type=expected_ct
+    )
+
+
 def test_is_expected_content_type_non_json_match_exact():
     expected_ct = "text/javascript"
     response_ct = "text/javascript"