diff --git a/CHANGES b/CHANGES
index 7d321d9c53..02066bfd83 100644
--- a/CHANGES
+++ b/CHANGES
@@ -1,3 +1,7 @@
+6155.	[bug]		Treat ISC_R_INVALIDPROTO as a networking error
+			in the dispatch code to avoid retrying with the
+			same server. [GL #4005]<
+
 6149.	[test]		As a workaround, include an OpenSSL header file before
 			including cmocka.h in the unit tests, because OpenSSL
 			3.1.0 uses __attribute__(malloc), conflicting with a
diff --git a/doc/notes/notes-current.rst b/doc/notes/notes-current.rst
index f432e1ef0e..212fdb166b 100644
--- a/doc/notes/notes-current.rst
+++ b/doc/notes/notes-current.rst
@@ -35,7 +35,9 @@ Feature Changes
 Bug Fixes
 ~~~~~~~~~
 
-- None.
+- When ISC_R_INVALIDPROTO (ENOPROTOOPT, EPROTONOSUPPORT) is returned from
+  libuv, treat it as a network failure, mark the server as broken and don't
+  try again. :gl:`#4005`
 
 Known Issues
 ~~~~~~~~~~~~
diff --git a/lib/dns/resolver.c b/lib/dns/resolver.c
index 9545560bfa..b09813d444 100644
--- a/lib/dns/resolver.c
+++ b/lib/dns/resolver.c
@@ -8178,6 +8178,7 @@ rctx_dispfail(respctx_t *rctx) {
 	case ISC_R_NETUNREACH:
 	case ISC_R_CONNREFUSED:
 	case ISC_R_CONNECTIONRESET:
+	case ISC_R_INVALIDPROTO:
 	case ISC_R_CANCELED:
 	case ISC_R_SHUTTINGDOWN:
 		rctx->broken_server = rctx->result;
diff --git a/lib/isc/include/isc/result.h b/lib/isc/include/isc/result.h
index 1b5941178c..5d5195b38f 100644
--- a/lib/isc/include/isc/result.h
+++ b/lib/isc/include/isc/result.h
@@ -95,6 +95,7 @@ typedef enum isc_result {
 	ISC_R_TLSBADPEERCERT, /*%< TLS peer certificate verification failed */
 	ISC_R_HTTP2ALPNERROR, /*%< ALPN for HTTP/2 failed */
 	ISC_R_DOTALPNERROR,   /*%< ALPN for DoT failed */
+	ISC_R_INVALIDPROTO,   /*%< invalid protocol */
 
 	DNS_R_LABELTOOLONG = 1 << 16,
 	DNS_R_BADESCAPE,
diff --git a/lib/isc/netmgr/uverr2result.c b/lib/isc/netmgr/uverr2result.c
index 99ed1b3aa9..9f16ea8271 100644
--- a/lib/isc/netmgr/uverr2result.c
+++ b/lib/isc/netmgr/uverr2result.c
@@ -90,13 +90,15 @@ isc___nm_uverr2result(int uverr, bool dolog, const char *file,
 		return (ISC_R_MAXSIZE);
 	case UV_ENOTSUP:
 		return (ISC_R_FAMILYNOSUPPORT);
+	case UV_ENOPROTOOPT:
+	case UV_EPROTONOSUPPORT:
+		return (ISC_R_INVALIDPROTO);
 	default:
 		if (dolog) {
-			UNEXPECTED_ERROR(
-				file, line,
-				"unable to convert libuv "
-				"error code in %s to isc_result: %d: %s",
-				func, uverr, uv_strerror(uverr));
+			UNEXPECTED_ERROR("unable to convert libuv error code "
+					 "in %s (%s:%d) to isc_result: %d: %s",
+					 func, file, line, uverr,
+					 uv_strerror(uverr));
 		}
 		return (ISC_R_UNEXPECTED);
 	}
diff --git a/lib/isc/result.c b/lib/isc/result.c
index 24a0053511..f01df3e817 100644
--- a/lib/isc/result.c
+++ b/lib/isc/result.c
@@ -94,6 +94,7 @@ static const char *description[ISC_R_NRESULTS] = {
 	[ISC_R_TLSBADPEERCERT] = "TLS peer certificate verification failed",
 	[ISC_R_HTTP2ALPNERROR] = "ALPN for HTTP/2 failed",
 	[ISC_R_DOTALPNERROR] = "ALPN for DoT failed",
+	[ISC_R_INVALIDPROTO] = "invalid protocol",
 
 	[DNS_R_LABELTOOLONG] = "label too long",
 	[DNS_R_BADESCAPE] = "bad escape",