Ole Gunnar Solskjaer's side opened their European campaign with a memorable 2-1 victory over Paris Saint-Germain last week, but the Red Devils were then held to a goalless draw by Chelsea on their own turf in Saturday's Premier League fixture.
United also have another crunch match in the league against Arsenal to come on Sunday, meaning that Solskjaer has plenty to ponder when it comes to team selection for the visit of Leipzig.
Here, Sports Mole takes a look at how the Red Devils could line up for Wednesday's showdown with the Bundesliga side.
Solskjaer has little to worry about in terms of injuries, with the only players sidelined for the Red Devils being Phil Jones, Eric Bailly and Jesse Lingard, none of whom would have been likely to start here anyway.
United reverted back to their more familiar 4-2-3-1 formation against Chelsea, but given how well the three-man defence worked against PSG last week, Solskjaer may be tempted to switch back to that system for the visit of an equally-strong Leipzig side.
Such a formation is likely to see Axel Tuanzebe come back into the side following his stellar performance against the Ligue 1 champions, and the 22-year-old could be partnered by Victor Lindelof and Luke Shaw should Harry Maguire be given a much-needed rest.
Aaron Wan-Bissaka and Alex Telles are sure to keep their places out wide, but Solskjaer has a number of dilemmas in the middle of the park with Paul Pogba and Nemanja Matic vying for starting roles in this encounter.
However, familiar faces in Fred and Scott McTominay could be given the nod once again on Wednesday evening, while the number 10 role could be occupied by Donny van de Beek, who has struggled for starts since his arrival, but Bruno Fernandes may be rested with Sunday's match against Arsenal in mind.
Up top, Marcus Rashford has become renowned for his work off the pitch as much as he has on it recently, but as is the case with Fernandes, Solskjaer will not want to take any risks over the forward's fitness.
United's selection concerns on the attacking front are eased by the fact that Anthony Martial is available for this one despite a domestic suspension, and the Frenchman could form a two-man strike force with Edinson Cavani, who very nearly marked his debut for United with a goal against Chelsea at the weekend.