The 0-0 draw in the reverse leg of the fixture sees United go into the decider as favourites, having lost just once on home soil so far this season.
Sevilla themselves have become something of European specialists lately, however, having picked up three back-to-back Europa League titles from 2013-14 to 2015-16.
But will Vincenzo Montella and his side come out on top against the current champions and prove they belong amongst the European elite?
|Game||Manchester United vs Sevilla|
|Date||Tuesday, March 13|
|Time||19:45 GMT / 14:45 ET|
|Stream (US only)||fubo TV (7-day free trial)|
TV Channel & Live Stream
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|US TV channel||Online stream|
|Fox Sports 1||fubo TV (7-day free trial)|
In the United Kingdom (UK), the game can be watched live on TV on BT Sport 2 and it can be streamed live online using the BT Sport app.
|UK TV channel||Online stream|
|BT Sport 2||BT Sport app|
Squads & Team News
|Position||Manchester United players|
|Goalkeepers||De Gea, Romero, Pereira|
|Defenders||Lindelof, Bailly, Jones, Rojo, Smalling, Blind, Shaw, Valencia, Darmian, Borthwick-Jackson|
|Midfielders||Pogba, Mata, Lingard, Carrick, Young, Herrera, Fellaini, Matic, McTominay|
|Forwards||Alexis, Lukaku, Martial, Rashford|
Paul Pogba has been included in the squad despite missing United's 2-1 victory over Liverpool at the weekend, though he was unable to train with his team-mates on Monday as Mourinho's side prepared for Sevilla's visit.
The United boss has confirmed Anthony Martial is available for selection, while Jesse Lingard will serve a one-match European ban should he pick up another yellow card here.
Potential Man United starting XI: De Gea; Valencia, Bailly, Smalling, Young; Matic, McTominay; Mata, Lingard, Alexis; Lukaku.
|Defenders||Corchia, Layun, Kjaer, Lenglet, Carrico, Arana, Escudero, Pareja, Mercado|
|Midfielders||Mesa, Banega, Correa, Geis, Pizarro, N'Zonzi, Navas, Sarabia, Ganso, Vazquez|
|Forwards||Ben Yedder, Muriel, Ramirez, Nolito|
Former Manchester City winger Jesus Navas will miss the trip to Old Trafford because of injury, while Sebastien Corchia is also unavailable.
Miguel Layun is ineligible but Simon Kjaer is set to return to the starting XI.
Potential Sevilla starting XI: Rico; Mercado, Kjaer, Lenglet, Escudero; N'Zonzi, Banega; Sarabia, Vazquez, Correa; Luis Muriel.
Betting & Match Odds
Manchester United are favourites to progress, with dabblebet placing them at 6/10.
The Liga side are a 9/2 bet and a draw is 14/5.
Pep Guardiola's Premier League dominance with Man City has seen Mourinho turn his attention to cup competitions, with the FA Cup and Champions League trophies his focus.
Following United's 2-1 win over rivals Liverpool on Saturday, Mourinho said: “Sevilla and Brighton [FA Cup quarter-final opponents] are more important than Liverpool. Liverpool is Liverpool, Liverpool is a big match, Liverpool is a match against a valid competitor for the top four, but nothing is decided.
“We have eight more matches to play so 24 points to play for, but Brighton is die or live and Sevilla is die or live so the next two are much more important than the last one.”
United have lost just once at Old Trafford this season, against neighbours City in December, and will be hoping their home advantage will see them secure a spot in the quarter-final draw on Friday following a 0-0 draw in the first leg of the tie.
Sevilla have only lost one of their last six fixtures, and have scored in every European match so far this season.
The Spanish outfit have never reached the quarter-finals of the Champions League, though, and face a difficult evening on Tuesday.