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The Red Devils came from 2-1 down to trounce their Italian opponents 6-2 seven days ago and will take great confidence into the Europa League semi-final second leg.
Hot off the heels of announcing former Man Utd man Jose Mourinho as their next manager, Roma are a struggling side who sit seventh in Serie A.
This game is all that is left of their season, so they will undoubtedly give it everything to try and turn the huge deficit around.
But Ole Gunnar Solskjaer will have his eye on a first trophy for the club, so his side will not take this one lightly.
Here’s everything you need to know ahead of the match.
When is it?
The match will kick-off at 8pm BST on Thursday 5 May.
How can I watch?
It will be shown live on BT Sport 3 and BT Sport Ultimate, with coverage getting underway from 7:15pm. The match is also available to stream for its customers on the BT Sport app and website.
What is the team news?
Phil Jones and Anthony Martial were the only members of Solskjaer’s squad unavailable for the Liverpool match last weekend which ended up being postponed.
There are no other injury concerns for the Red Devils, so they should be able to field a full strength team.
Meanwhile, Roma suffered three first half casualties in the first leg last week, losing keeper Pau Lopez, Jordan Veretout and Leonardo Spinazzola.
And Lopez is out for the remainder of the season, while Veretout aand Spinazzola also doubtful for the second leg.
Manchester United: 17/20
Roma XI: Peres; Smalling, Cristante, Ibanez; Karsdorp, Diaware, Mirante, Villar; Pellegrini, Mkhitaryan; Dzeko
Man Utd XI: De Gea; Wan-Bissaka, Lindelof, Maguire, Shaw; McTominay, Fred; Rashford, Fernandes, Pogba; Cavani
It will take a miracle for Roma to turn this tie around, especially given Manchester United’s remarkably impressive form on the road. The Italians caved in towards the end of the first leg and will want to show that they have more resolve than what they showed at Old Trafford. But the pace, creativity and ruthlessness is with United and they should have enough to win this one. 2-1 Man Utd.