The forward missed Saturday's 3-1 win over Liverpool after suffering a hamstring injury in training, and manager Louis van Gaal admits it is unlikely his captain will make the trip to the Netherlands.
The former Barcelona coach is more confident Rooney will be fit to take on Southampton on September 20 in their next domestic outing.
"He is injured so we have to take care of him," he told MUTV. "I think he is very important for us and I don’t to take any risks so that’s why he doesn’t play [against Liverpool].
"I don’t think he will play against PSV Eindhoven, but maybe he shall play at Southampton. We have to wait and see if he can play against PSV because we still have three days to go."
United's clash with the Eredivisie champions marks their return to Champions League group stages having missed out last season, with Rooney's hat-trick against Club Brugge helping them through the play-off round.