The England international picked up an injury during Man United's FA Cup semi-final against Coventry City on Sunday, and he is absent from the squad against the side at the bottom of the Premier League table.
Alejandro Garnacho and Bruno Fernandes are both fit despite injury scares at the weekend, while Scott McTominay drops down to the bench after being forced off against the Championship side last time out.
Antony and Christian Eriksen come into the side, with Casemiro again required in the middle of the defence due to the team's injury problems in that area of the field.
Sofyan Amrabat is back on the bench after missing out against Coventry through injury, with Kobbie Mainoo featuring alongside Eriksen in the middle of midfield.
As for Sheffield United, Oliver Arblaster, 20, will captain the visitors at Old Trafford.
Head coach Chris Wilder has shuffled his pack from the 4-1 loss to Burnley last time out, with Wes Foderingham back in goal, while Cameron Archer features in attack, as Oli McBurnie is injured.
Mason Holgate also returns at the back, and there is a spot in the side for Gustavo Hamer, who has overcome a muscular problem.
Manchester United: Onana; Dalot, Maguire, Casemiro, Wan-Bissaka; Mainoo, Eriksen; Antony, Fernandes, Garnacho; Hojlund
Subs: Bayindir, Amass, Jackson, Ogunneye, Amad, Amrabat, Forson, McTominay, Wheatley
Sheffield United: Foderingham; Holgate, Ahmedhodzic, Trusty; Bogle, Hamer, Arblaster, Osborn, Brooks; Brereton Diaz, Archer
Subs: Grbic, Norwood, Souza, Slimane, Larouci, McAtee, Curtis, Osula, Hampson