diff --git a/internal/functions/serve/serve.go b/internal/functions/serve/serve.go
index dc82f532e4..38ca9f7e2e 100644
--- a/internal/functions/serve/serve.go
+++ b/internal/functions/serve/serve.go
@@ -223,6 +223,16 @@ EOF
 		container.HostConfig{
 			Binds:        binds,
 			PortBindings: portBindings,
+			Resources: container.Resources{
+				// Raise nofile to accommodate FD usage from many concurrent Deno isolates (see #5151).
+				Ulimits: []*container.Ulimit{
+					{
+						Name: "nofile",
+						Soft: 65536,
+						Hard: 65536,
+					},
+				},
+			},
 		},
 		network.NetworkingConfig{
 			EndpointsConfig: map[string]*network.EndpointSettings{