With both teams winning every game in the competition since La Real's 1-0 victory at Old Trafford in the opener, Erik ten Hag's men need to triumph by two or more goals in order to usurp the San Sebastian side as group winners.
The runners-up face a play-off against one of the third-placed clubs in the Champions League, with the draw for that round taking place on Monday.
The news from the camp is that Victor Lindelof is available again. The defender was ill last weekend, and missed the win over West Ham United.
Antony and Anthony Martial will remain at Carrington, to continue with their individual training work, while Jadon Sancho is ill.