Of the starters from the 2-0 FA Cup win over Brighton & Hove Albion a fortnight ago, Sergio Romero is out injured while Eric Bailly, Luke Shaw, Scott McTominay - who sustained a calf problem over the international break - and Anthony Martial are among the replacements.
Also on the bench at Old Trafford is Ander Herrera, returning after several weeks out with injury.
Carlos Carvalhal, meanwhile, makes four changes to the Swans side that fell to a 3-0 loss against Tottenham Hotspur as they try to widen the current three-point gap between themselves and the relegation zone.
Lukasz Fabianski takes his place in goal, as Andy King, Andre Ayew and Federico Fernandez also come in. Kristoffer Nordfeldt, Kyle Bartley, Tom Carroll and Tammy Abraham all drop to the bench to make way.
Manchester United: De Gea; Young, Lindelof, Smalling, Valencia; Matic, Pogba; Mata, Lingard, Sanchez; Lukaku
Subs: Pereira, Bailly, Martial, Rashford, Herrera, Shaw, McTominay
Swansea City: Fabianski, Van Der Hoorn, Mawson, Fernandez, Olsson, Naughton, Clucas, King, Ki, Dyer, A Ayew
Subs: Nordfeldt, Abraham, Narsingh, Carroll, Routledge, Bartley, Roberts
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