diff --git a/changelog.d/9070.bugfix b/changelog.d/9070.bugfix
new file mode 100644
index 0000000000..72b8fe9f1c
--- /dev/null
+++ b/changelog.d/9070.bugfix
@@ -0,0 +1 @@
+Fix `JSONDecodeError` spamming the logs when sending transactions to remote servers.
diff --git a/synapse/http/matrixfederationclient.py b/synapse/http/matrixfederationclient.py
index b261e078c4..b7103d6541 100644
--- a/synapse/http/matrixfederationclient.py
+++ b/synapse/http/matrixfederationclient.py
@@ -174,6 +174,16 @@ async def _handle_json_response(
         d = timeout_deferred(d, timeout=timeout_sec, reactor=reactor)
 
         body = await make_deferred_yieldable(d)
+    except ValueError as e:
+        # The JSON content was invalid.
+        logger.warning(
+            "{%s} [%s] Failed to parse JSON response - %s %s",
+            request.txn_id,
+            request.destination,
+            request.method,
+            request.uri.decode("ascii"),
+        )
+        raise RequestSendFailed(e, can_retry=False) from e
     except defer.TimeoutError as e:
         logger.warning(
             "{%s} [%s] Timed out reading response - %s %s",
diff --git a/tests/http/test_fedclient.py b/tests/http/test_fedclient.py
index 212484a7fe..9c52c8fdca 100644
--- a/tests/http/test_fedclient.py
+++ b/tests/http/test_fedclient.py
@@ -560,4 +560,4 @@ class FederationClientTests(HomeserverTestCase):
         self.pump()
 
         f = self.failureResultOf(test_d)
-        self.assertIsInstance(f.value, ValueError)
+        self.assertIsInstance(f.value, RequestSendFailed)