United are within touching distance of a seventh major European final after last week's narrow 1-0 win in Galicia.
The Reds hopes of Champions League qualification via the league look over, so it's all or nothing in Europe now ahead of this season defining semi-final.
Marcus Rashford's superb set piece separates the sides and, despite the challenge of a strong Celta Vigo side, the Reds remain firm favourites to progress to the final.
Eduardo Berizzo's out-of-form team have lost their last five in all competitions, and United, in stark contrast to our indifferent home league form, boast an imposing 100% Old Trafford European record this term.
Sitting comfortably in mid-table in La Liga, Celta have never reached a European final and, like United, have been resting players in preparation for this tie.
With the Reds bidding to win the only major trophy missing from the club's collection, and claim the Champions League place that comes with victory, Ajax look set to provide the opposition on 24 May.
The Dutch giants hold a commanding 4-1 lead over Lyon in the other last four tie and barring a very unlikely turnaround, will progress to the Stockholm showpiece.
Jose Mourinho will restore several of the side's key men, having rotated his side at Arsenal in preparation for this one.
Paul Pogba, Eric Bailly, Daley Blind, Antonio Valencia and Rashford are all likely to return having been rested on Sunday, and Marouane Fellaini is also available.
Ashley Young became United's latest injury casualty when he limped off with a hamstring tear in the first leg shortly after coming on.
He is likely to miss the rest of the campaign and joins Zlatan Ibrahimovic, Marcos Rojo, Tim Fosu - Mensah and Luke Shaw on the sidelines.
Mourinho said that his decision to prioritise Europe over league duties was common sense and the only way to manage United's hectic fixture list.
He said: "It is not a gamble, seventeen matches in six weeks with 16 players is impossible.
"It was a simple decision, the Europa League is a trophy and that is what we want, not to finish fourth or fifth so it is the only way.
"It's a decision with common sense, we are giving everything so it is no problem.
"For Celta it is the most important match they will ever play, and for us a European final would be beautiful.
"It doesn't matter what happened before, what's important is what happens next."
Form guide: United W W D D W L Celta Vigo D L L L L L
Match odds: United 15/8 Draw 10/3 Celta Vigo 33/1
Referee: Romanian ref Ovidiu Hategan is the man in the middle