diff --git a/changelog.d/10592.bugfix b/changelog.d/10592.bugfix
new file mode 100644
index 0000000000..efcdab1136
--- /dev/null
+++ b/changelog.d/10592.bugfix
@@ -0,0 +1 @@
+Fix a bug introduced in v1.37.1 where an error could occur in the asyncronous processing of PDUs when the queue was empty.
diff --git a/synapse/federation/federation_server.py b/synapse/federation/federation_server.py
index 0385aadefa..78d5aac6af 100644
--- a/synapse/federation/federation_server.py
+++ b/synapse/federation/federation_server.py
@@ -972,13 +972,18 @@ class FederationServer(FederationBase):
         # the room, so instead of pulling the event out of the DB and parsing
         # the event we just pull out the next event ID and check if that matches.
         if latest_event is not None and latest_origin is not None:
-            (
-                next_origin,
-                next_event_id,
-            ) = await self.store.get_next_staged_event_id_for_room(room_id)
-            if next_origin != latest_origin or next_event_id != latest_event.event_id:
+            result = await self.store.get_next_staged_event_id_for_room(room_id)
+            if result is None:
                 latest_origin = None
                 latest_event = None
+            else:
+                next_origin, next_event_id = result
+                if (
+                    next_origin != latest_origin
+                    or next_event_id != latest_event.event_id
+                ):
+                    latest_origin = None
+                    latest_event = None
 
         if latest_origin is None or latest_event is None:
             next = await self.store.get_next_staged_event_for_room(