Rooney has been out of action in recent days due to a hamstring injury.
Meanwhile, Phil Jones has returned to training after suffering from mild thrombosis.
“Shaw’s injury is a big loss but Rooney is fit to play [vs Southampton] and Jones has trained with the group,” van Gaal said.
Rooney’s return may mean Anthony Martial drops to the substitute’s bench against Southampton.
The young Frenchman started against PSV Eindhoven earlier this week and impressed but van Gaal will be keen not to throw him into the deep end too early. That being said, there is the possibility that Rooney could play in the No.10 role behind Martial.