diff --git a/changelog.d/8465.bugfix b/changelog.d/8465.bugfix
new file mode 100644
index 0000000000..73f895b268
--- /dev/null
+++ b/changelog.d/8465.bugfix
@@ -0,0 +1 @@
+Don't attempt to respond to some requests if the client has already disconnected.
\ No newline at end of file
diff --git a/synapse/http/server.py b/synapse/http/server.py
index 09ed74f6ce..00b98af3d4 100644
--- a/synapse/http/server.py
+++ b/synapse/http/server.py
@@ -651,6 +651,11 @@ def respond_with_json_bytes(
     Returns:
         twisted.web.server.NOT_DONE_YET if the request is still active.
     """
+    if request._disconnected:
+        logger.warning(
+            "Not sending response to request %s, already disconnected.", request
+        )
+        return
 
     request.setResponseCode(code)
     request.setHeader(b"Content-Type", b"application/json")
diff --git a/synapse/rest/media/v1/_base.py b/synapse/rest/media/v1/_base.py
index 6568e61829..67aa993f19 100644
--- a/synapse/rest/media/v1/_base.py
+++ b/synapse/rest/media/v1/_base.py
@@ -213,6 +213,12 @@ async def respond_with_responder(
         file_size (int|None): Size in bytes of the media. If not known it should be None
         upload_name (str|None): The name of the requested file, if any.
     """
+    if request._disconnected:
+        logger.warning(
+            "Not sending response to request %s, already disconnected.", request
+        )
+        return
+
     if not responder:
         respond_404(request)
         return