Casemiro is in line for his Manchester United debut at Southampton while manager Erik ten Hag has to decide whether to recall Cristiano Ronaldo.
French striker Anthony Martial's injury problems have continued with the striker suffering an Achilles injury and facing an unspecified spell on the sidelines.
And that means that ten Hag, keen to build on Monday's impressive win over Liverpool, must decide whether to hand a start to Ronaldo, who is still angling to leave Old Trafford before the window closes next week.
Against Liverpool neither Ronaldo nor Martial started - with Marcus Rashford given a central attacking role - which adds to the complexity of ten Hag's selections.