United face the trip to the Estadio Ramon Sanchez Pizjuan, with a hostile reception no doubt in store.
The Spanish side have gained a reputation for their strong performances in European competition in recent years albeit largely in the Europa League and Mourinho is convinced that his side will be put to the test and denied suggestions that United are heavy favourites for the game.
"With Sevilla, I don't think it's possible to score many goals," Mourinho told United's in-house TV channel 'MUTV'. "I think the game is going to be really competitive.
"They can say what they want; they can be nice to us and say we are favourites - that means absolutely nothing.
"I think I prefer to say they have good players and a good team and a good mentality for the knockout matches. Sevilla is a club of cups and now they have the chance to play in the biggest competition of all, so the motivation is obviously even bigger.
"For me, the word 'favourite' or 'not favourite' means nothing. They have good defensive organisation; they defend with everybody. [Sevilla boss Vincenzo] Montella is Italian and Italian coaches know how to organise their teams very compact from the defensive point of view.
"I can see easily now the distances between the wingers and the full-backs are much shorter. The wingers drop back to compact with the full-backs; not like in England.
Never one to miss an opportunity, Mourinho also took the chance to criticise English pundits, saying: "In England, some experts that never sit on the bench say wingers shouldn't defend and the midfield players should only attack. But that's only in England in this moment, with this generation of experts."
Finally, Mourinho admitted that the hostility of the locals and Sevilla's enviable Cup record could play a role in the outcome of the match.
"It's a really difficult stadium to play at because it's a stadium where the fans love the knock-out competition," he admitted. "They are called a knock-out team because they are normally very successful in the domestic cups, and especially in the Europa League.
"The crowd plays the game. They don't come here just to watch, they come here to play the game and put lots of pressure on the opponent and the referee's decisions."