The Red Devils have a number of injury and fitness concerns heading into the match, not helped by two more players picking up knocks in last weekend's friendly defeat to Bayern Munich.
Jose Mourinho will be forced to shuffle his pack for the first match of the season, but he still has a number of big-name players to choose from.
Here, Sports Mole predicts how the Portuguese will set out his side for the curtain-raising fixture.
Out: Nemanja Matic, Antonio Valencia, Diogo Dalot, Marcos Rojo
Doubts: Marouane Fellaini, Jesse Lingard, Ashley Young, Paul Pogba, Phil Jones, Marcos Rashford, Eric Bailly, Ander Herrera, Romelu Lukaku
Rashford cut short his post-World Cup holiday in order to get some minutes under his belt in United's final pre-season friendly against Bayern, which ended in a 1-0 loss at the Allianz Arena, and could be handed a start through the middle in the possible absence of Romelu Lukaku.
Mourinho confirmed during the club's tour of the United States that Matic had undergone minor surgery that will rule him out for at least the opening match, while Valencia, summer signing Dalot and Everton-linked Rojo are all carrying injuries.
Matteo Darmian will be one of the biggest winners of the injury crisis, with a right-back berth there for the taking, while Luke Shaw is favourite to start on the left after being given an extended run in the side.
Elsewhere, Bailly picked up a minor injury against Bayern but should be OK to start in the heart of defence, and Herrera will also be required in a depleted central midfield, where Andreas Pereira may finally be given a chance to shine.