Jose Mourinho's side go into the match having turned their early-season slump around with back-to-back wins in the Premier League, and are now looking to make it three in a row for the first time since April.
The three-time European champions were knocked out in the last 16 of the competition in 2017-18, and also lost in Switzerland during the group stages when they fell to a 1-0 defeat to Basel.
Here, Sports Mole looks at how they could line up to avoid a similar result on Wednesday.
Out: Phil Jones (hamstring), Ander Herrera (ankle), Marcos Rojo (knock), Antonio Valencia (knee), Jesse Lingard (not in squad)
Mourinho has confirmed that captain Valencia will not feature on Wednesday due to concerns over how his knee would react to an artificial pitch, which could pave the way for summer signing Diogo Dalot to make his debut for the club at right-back.
Luke Shaw should return on the left after recovering from concussion suffered during the international break, while Mourinho now appears to have settled on the centre-back partnership of Chris Smalling and Victor Lindelof - at least in the continued absence of Jones and Rojo.