Although a visit to Old Trafford may appear to be a daunting prospect for many teams, for Sevilla, who are renowned for their success in the Europa League, the trip represents a much-needed respite from the rigors of their domestic campaign.
The Andalucians, led by Jose Luis Mendilibar – their third coach of the season – have been mired in a relegation scrap in La Liga, but find themselves on more familiar ground in Europe.
Record six-time Europa League champions, Sevilla's players are more accustomed to battling for silverware than survival, and have shown signs of improvement under Mendilibar.
That give them some hope of overcoming Erik ten Hag's three-time European Cup winners in the quarterfinal, which would earn redemption with supporters after a year to forget.
"I'm convinced that, in Europe, Sevilla are respected more than in La Liga, because of what they have done in the Europa League, with a lot of titles quite recently," said Mendilibar in March after taking over from Jorge Sampaoli.
"In Manchester they will feel they are favorites, but with respect for Sevilla."
Behind Sevilla, Inter Milan, Liverpool, Juventus and Atletico Madrid have each won the trophy three times, while Manchester United lifted it once, in 2017.
Despite holding their own against such esteemed company on the continent, domestically Sevilla have fallen and are currently 13th, five points above the bottom three.
"(We're doing) quite well in European competition, unlike the national league, sadly," said veteran midfielder Ivan Rakitic told UEFA.
"But we know Sevilla's overall history in Europe."
Sevilla's struggle started when the club's poor financial state forced them to sell key defenders Jules Kounde and Diego Carlos to Barcelona and Aston Villa respectively, ripping in half one of the continent's sturdiest backlines.
A bet on former Real Madrid playmaker Isco did not work, with the player leaving in December by mutual consent.
Despite a poor finish last season the club decided to keep Julen Lopetegui at the helm, but replaced him in October after just one win in 10 games.
A 4-1 hammering by Borussia Dortmund in the Champions League was the final straw, and Sampaoli was appointed for his second spell at the club.
The Argentine coach helped the team to a draw in Dortmund and a win over Copenhagen to ensure they would drop into the Europa League, rather than out of Europe entirely.
Despite overcoming PSV and Fenerbahçe to set up a quarterfinal clash with Manchester United, Sampaoli's dismal league form saw him removed with the team 14th, just two points above the drop zone.
Mendilibar is operating with a back-to-basics, more direct style. It paid instant dividends with a 2-0 win at relegation rivals Cadiz in his first game.
They moved two goals up against Celta Vigo last Friday in his second match, before the visitors struck twice late on at the Ramon Sanchez-Pizjuan to push Sevilla back into the scrap.
Morocco international Youssef En-Nesyri has found his shooting boots and is an aerial threat, which could be useful at Old Trafford.
Lucas Ocampos, back from loan at Ajax, is another explosive option who can give Mendilibar's side a fighting chance of a result on the road, along with the tricky Bryan Gil, on loan from Tottenham.
Sevilla will not be able to call on midfield powerhouse Pape Gueye, who is not registered for the competition, while United will have Casemiro available after his Premier League suspension.
"Here in the city, people say the Europa League is Sevilla's competition," added Rakitic.
"It's something which belongs to us because we have won it six times in the last 15 or so years.
"Respect to everyone who's also won it, but it is somehow our competition."
Manchester United however have received a major blow to their squad as their talisman Marcus Rashford will miss Thursday's tie with Sevilla after being ruled out for "a few games" with a muscle injury he picked up against Everton on Saturday.
The 25-year-old has been in fine form for Erik ten Hag's side in recent months but limped out of the 2-0 Premier League win over the Toffees.
"Marcus Rashford will be unavailable for Thursday's UEFA Europa League quarterfinal game against Sevilla because of a muscle injury," United said in a statement on Wednesday.
"The forward was withdrawn in the 80th minute of Saturday's 2-0 Premier League win over Everton at Old Trafford and immediately headed to the dressing room for treatment.
"Subsequent assessment of the injury suggested that Marcus will be unavailable for a few games, but is expected to be back for the season run-in."
