The tie is finely poised at 2-2 following a dramatic conclusion to the first game in France last week. United thought they had come from behind to earn a valuable first-leg lead, but a mistake in injury time from Andre Onana gifted Rayan Cherki a last-gasp equaliser.
As a result, both sides know they have to win this evening to avoid extra time and possibly penalties.
Lyon, meanwhile, beat Auxerre away from home on Sunday to remain in the hunt for Champions League qualification through their position in Ligue 1.
Date, kick-off time and venue
Manchester United vs Lyon is scheduled for a 8pm BST kick-off on Thursday, April 17, 2025.
The match will take place at Old Trafford, Manchester.
Where to watch Manchester United vs Lyon
TV channel: In the UK, the game will be televised live on TNT Sports.
Live stream: TNT Sports subscribers can also catch the contest live online via the Discovery+ app and website.
Live blog: You can follow all the action on matchday via Standard Sport’s live blog!
Manchester United vs Lyon team news
While Jonny Evans has returned to training after a long lay-off, this game comes too soon for the defender to be involved. Matthijs de Ligt, Amad Diallo, Lisandro Martinez and Toby Collyer are all out and Ayden Heaven has suffered a setback.
Lyon can also call upon the likes of former Arsenal pair Alexandre Lacazette and Ainsley Maitland-Niles. Belgium’s Malick Fofana is back in the squad after missing the first leg, but fellow winger Ernest Nuamah remains injured.
Injury blow: Manchester United will be without Joshua Zirkzee for the remainder of the season
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Manchester United vs Lyon prediction
Losing Zirkzee is a blow for United, especially because Rasmus Hojlund has been out of sorts. Having said that, the striker has tended to save his better performances for the Europa League.
Similarly, United have found a formula in Europe that has seen them remain unbeaten in the competition up until this point, winning all their home games under Amorim. That record looks set to continue tonight.
Manchester United to win, 2-1.
Head to head (h2h) history and results
Manchester United wins: 2
Manchester United vs Lyon odds
Manchester United to qualify: 1/3
Odds via Betfair (subject to change).