After breezing past Real Betis 4-1 in the last 16, Erik ten Hag's men will be travelling back to Seville to take on Europa kings Sevilla.
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Despite the Spanish side's struggles in LaLiga, where they find themselves in an unexpected relegation battle, there are still few teams you'd rather face than the record six-time winners.
Led by Wolves boss Julen Lopetegui at the start of the season, he was fired and replaced by returning manager Jorge Sampaoli, without much improvement in the table.
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Even with their issues, Sevilla still boast an impressive squad, featuring Argentina World Cup winners Gonzalo Montiel, Marcos Acuna and Papu Gomez.
They also have Moroccan heroes Yassine Bounou and Youssef En-Nesryi, but one name will stand out to United fans more than any other.
Brazilian left back Alex Telles is on loan from United, and will be eligible to play in the tie.
Signed from Porto for £15million in 2020 as one of the best players in the Portuguese league, Telles never nailed down a spot at Old Trafford, but some fans are still worried about him returning to haunt them.
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One fan tweeted: "The f*** am I supposed to do when Telles scores a wonder goal at OT to send Sevilla through then?"
Another added: "Alex Telles about to drop a Roberto Carlos type of performance against us."
A third wrote: "Telles screamer in the 34th minute?"
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However, not everyone is worried about facing the 30-year-old as one supporter remarked: "Loser of Manchester United vs Sevilla gets to keep Alex Telles."
Another said: "Telles vs Antony, he might actually beat his man for once."
United's record against Sevilla doesn't make for great reading if you're a Red Devils fan, either.
The Spaniards are a bit of a bogey team for the Premier League giants - from the three games played between the teams, United have zero wins, two defeats and one draw.
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Sevilla also dumped United out of the 2018 edition of the Champions League, so they will be hoping for better fortune this time around - and that their own man, Telles, doesn't come back to bite them.