Another defeat on Wednesday could see them fall out of the qualification places, but they will enter the match as underdogs against a rampant Juve side including United's former talisman Cristiano Ronaldo.
Here, Sports Mole looks at how Jose Mourinho could set his side up for the match.
Having been dropped against Everton, Romelu Lukaku was absent from the squad entirely against Bournemouth at the weekend after picking up a minor injury in training.
The Belgian could be involved on Wednesday night, although whether he starts or not is another matter having now gone nine games without a goal for the club.
Alexis Sanchez led the line at the Vitality Stadium and is expected to carry out that role again, while Marcus Rashford may have also earned a start ahead of Juan Mata after coming off the bench to score a late winner.
For once, Anthony Martial's place looks the most concrete in the front three, with the French winger having now scored five goals in his last four league games.
Mourinho credited Ander Herrera with changing the game against Bournemouth and so could bring the Spaniard in from the start, while he is likely to remain unchanged at the back.