There are five changes in all to the XI that started the Manchester derby last weekend but Bruno Fernandes's unavailability is a concern with Atletico Madrid to come on Tuesday night in the Champions League round-of-16 second leg.
Raphael Varane and Cristiano Ronaldo are back in the side, with Edinson Cavani among the substitutes but, as expected, Scott McTominay has not made it due to a calf injury.
David De Gea starts, despite some talk he would not be playing, while Diogo Dalot and Marcus Rashford start in place of Aaron Wan-Bissaka and Anthony Elanga.
"Bruno is ill, unfortunately," confirmed Ralf before the game.