The Red Devils started brightly at the Ramon Sanchez-Pizjuan Stadium in the second leg of the Europa League quarter-finals coming off the back of blowing a two-goal lead in the final minutes at Old Trafford last week.
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But Erik ten Hag's side soon found themselves under pressure as David de Gea and Harry Maguire got in a muddle.
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The Red Devils goalkeeper passed the ball to his centre back on the edge of the D, but it appeared Maguire was given little warning and was quickly surrounded by three lingering Sevilla stars.
The Man United captain's touch ended up in the path of former Tottenham ace Erik Lamela, before striker Youssef En-Nesyri coolly slotted home into the bottom corner.
Reacting to the defensive error, Andy Townsend said on commentary for talkSPORT: "Disastrous for United…that is unbelievably poor, that really is. No need to concede a goal like that.
"Really careless from United, that is."
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It's so far been a nightmare tie for Maguire, who scored the second own goal in the first leg.
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However, Townsend and former Manchester United defender Gary Neville were quick to stress the England man is not solely to blame for Thursday night's error.
Townsened later added: "When you have the ball at your feet, you're the boss. Don't give it to Maguire if there's a danger of him losing the ball."
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While Neville tweeted: "Maguire will get battered but that pass from De Gea I wouldn't like."
Man United were then let off the hook when Sevilla had the ball in the net, only for VAR to rule the goal out for offside.
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But despite bringing on top scorer Marcus Rashford at the break for Jadon Sancho, Ten Hag's side found themselves 2-0 down after just two minutes with ex-Nottingham Forest loanee Loic Bade netting in the 47th minute.
And as if the first half mess up wasn't frustrating enough for Man United, it turns out De Gea still had another mistake in him.
Coming out of his box to clear Acuna's long clearance, the glovesman he got his first touch all wrong and the ball bounced to the opening scorer En-Nesyri once again who made no mistake from 30-yards out to make it 3-0, 5-2 on aggregate, and seal a spot in the semi-finals.