diff --git a/sentry_sdk/integrations/wsgi.py b/sentry_sdk/integrations/wsgi.py
index 1576e21a17..ea7ebbea4d 100644
--- a/sentry_sdk/integrations/wsgi.py
+++ b/sentry_sdk/integrations/wsgi.py
@@ -86,7 +86,7 @@ def __init__(
 
     def __call__(
         self, environ: "Dict[str, str]", start_response: "Callable[..., Any]"
-    ) -> "_ScopedResponse":
+    ) -> "Any":
         if _wsgi_middleware_applied.get(False):
             return self.app(environ, start_response)
 
@@ -135,6 +135,29 @@ def __call__(
         finally:
             _wsgi_middleware_applied.set(False)
 
+        # Within the uWSGI subhandler, the use of the "offload" mechanism for file responses
+        # is determined by a pointer equality check on the response object
+        # (see https://github.com/unbit/uwsgi/blob/8d116f7ea2b098c11ce54d0b3a561c54dcd11929/plugins/python/wsgi_subhandler.c#L278).
+        #
+        # If we were to return a _ScopedResponse, this would cause the check to always fail
+        # since it's checking the files are exactly the same.
+        #
+        # To avoid this and ensure that the offloading mechanism works as expected when it's
+        # enabled, we check if the response is a file-like object (determined by the presence
+        # of `fileno`), if the wsgi.file_wrapper is available in the environment (as if so,
+        # it would've been used in handling the file in the response).
+        #
+        # Even if the offload mechanism is not enabled, there are optimizations that uWSGI does for file-like objects,
+        # so we want to make sure we don't interfere with those either.
+        #
+        # If all conditions are met, we return the original response object directly,
+        # allowing uWSGI to handle it as intended.
+        if (
+            environ.get("wsgi.file_wrapper")
+            and getattr(response, "fileno", None) is not None
+        ):
+            return response
+
         return _ScopedResponse(scope, response)
 
 
diff --git a/tests/integrations/wsgi/test_wsgi.py b/tests/integrations/wsgi/test_wsgi.py
index a741d1c57b..1878be4866 100644
--- a/tests/integrations/wsgi/test_wsgi.py
+++ b/tests/integrations/wsgi/test_wsgi.py
@@ -6,7 +6,7 @@
 
 import sentry_sdk
 from sentry_sdk import capture_message
-from sentry_sdk.integrations.wsgi import SentryWsgiMiddleware
+from sentry_sdk.integrations.wsgi import SentryWsgiMiddleware, _ScopedResponse
 
 
 @pytest.fixture
@@ -500,3 +500,50 @@ def dogpark(environ, start_response):
     (event,) = events
 
     assert event["contexts"]["trace"]["origin"] == "auto.dogpark.deluxe"
+
+
+@pytest.mark.parametrize(
+    "has_file_wrapper, has_fileno, expect_wrapped",
+    [
+        (True, True, False),  # both conditions met → unwrapped
+        (False, True, True),  # no file_wrapper → wrapped
+        (True, False, True),  # no fileno → wrapped
+        (False, False, True),  # neither condition → wrapped
+    ],
+)
+def test_file_response_wrapping(
+    sentry_init, has_file_wrapper, has_fileno, expect_wrapped
+):
+    sentry_init()
+
+    response_mock = mock.MagicMock()
+    if not has_fileno:
+        del response_mock.fileno
+
+    def app(environ, start_response):
+        start_response("200 OK", [])
+        return response_mock
+
+    environ_extra = {}
+    if has_file_wrapper:
+        environ_extra["wsgi.file_wrapper"] = mock.MagicMock()
+
+    middleware = SentryWsgiMiddleware(app)
+
+    result = middleware(
+        {
+            "REQUEST_METHOD": "GET",
+            "PATH_INFO": "/",
+            "SERVER_NAME": "localhost",
+            "SERVER_PORT": "80",
+            "wsgi.url_scheme": "http",
+            "wsgi.input": mock.MagicMock(),
+            **environ_extra,
+        },
+        lambda status, headers: None,
+    )
+
+    if expect_wrapped:
+        assert isinstance(result, _ScopedResponse)
+    else:
+        assert result is response_mock