United will qualify from Group A with a victory, but it is the German side who have hit a rich vein of form, leapfrogging Borussia Dortmund into second place in the Bundesliga.
However, with Leverkusen star striker Sydney Sam sustaining an injury this past weekend ruling him out of the crucial tie, David Moyes will feel his side has a great chance to qualify now.
Defeat for United will mean a last-day shootout against Shakhtar Donetsk for progression.
Moyes has two key defensive options returning to the fold. Both Rafael and Nemanja Vidic took part in full training this morning. I expect the young Brazilian to come straight back into the first team. Chris Smalling had an excellent game against Arsenal but was less assured against Cardiff.
United have missed Rafael's ability to drive forward and the team craves this balance in attack.
Vidic's possible inclusion in the squad was put to rest as the United skipper did not make the flight to Germany. In the main Jonny Evans and Rio Ferdinand were solid at the weekend, but the question is, can Ferdinand play back-to-back matches?
If he was fit, I think Moyes would have played his captain with Evans. Smalling has a chance if Ferdinand is not deemed fresh enough.
Another key player who returned to training today was Phil Jones, who was injured on international duty.
I fully expect to see him thrown straight into central midfield alongside the experience of Ryan Giggs. With Marouane Fellaini suspended, I can see Moyes opting for this "brain and brawn" combination. Tom Cleverley struggled against Cardiff alongside Fellaini, leaving Giggs the manager's only option to freshen things up.
United's wide options are always incredibly subjective, but I can see Moyes opting for Ashley Young and Antonio Valencia. Young's popularity is at an all-time low with the United faithful, and his inclusion would cause panic attacks across social media and the pubs of Stretford.
However, the manager appears to be solid in his faith in 4-4-2 at the moment, and Young will give Evra the protection on the left that neither Adnan Januzaj or Shinji Kagawa would.
Valencia has enjoyed an improvement in form since the departure of Sir Alex Ferguson, but his effectiveness is still in question. However, like Young, he offers defensive protection that his competition does not.
United's biggest loss for the match is Robin Van Persie, who has failed to recover from injury. As a result I can see Shinji Kagawa playing behind Wayne Rooney in the striking positions. The return to Germany, where the Japanese international had his finest moments, is a fine excuse for Moyes to try the player in his preferred position.
The match is an opportunity to allow Kagawa to continue his improving form and give him the confidence he so clearly had lost at the start of this season.
Rooney is in fine scoring form and, with no Van Persie, I can see him getting the vote ahead of Danny Welbeck and Javier Hernandez.
The early months of David Moyes' reign have been fraught with trips and stumbles, so earning an early pass into the knockout phase will give him the respite he needs.
A defeat in Germany will compound the pressure he has been under after United's inconsistent displays, but a victory will afford him the opportunity to concentrate on a domestic Christmas charge in the Premier League.
My expected team: de Gea, Rafael, Evans, Ferdinand, Evra, Jones, Giggs, Valencia, Young, Kagawa, Rooney (4-4-1-1)