diff --git a/changelog.d/12163.misc b/changelog.d/12163.misc
new file mode 100644
index 0000000000000000000000000000000000000000..13de0895f5faebc60650bb69dcf41b1d8a47d1ef
--- /dev/null
+++ b/changelog.d/12163.misc
@@ -0,0 +1 @@
+Reduce number of DB queries made during processing of `/sync`.
diff --git a/synapse/storage/databases/main/deviceinbox.py b/synapse/storage/databases/main/deviceinbox.py
index 1392363de15a39978259641ce327029b843839a5..b4a1b041b1f82065670f45b047d956c15cdbd547 100644
--- a/synapse/storage/databases/main/deviceinbox.py
+++ b/synapse/storage/databases/main/deviceinbox.py
@@ -298,6 +298,9 @@ class DeviceInboxWorkerStore(SQLBaseStore):
                 # This user has new messages sent to them. Query messages for them
                 user_ids_to_query.add(user_id)
 
+        if not user_ids_to_query:
+            return {}, to_stream_id
+
         def get_device_messages_txn(txn: LoggingTransaction):
             # Build a query to select messages from any of the given devices that
             # are between the given stream id bounds.