United only qualified for the competition by winning the Europa League last season, but they successfully reached the knockout stages and are favourites to progress over two legs against a Sevilla side which has never reached the quarter-finals of the Champions League before.
The first leg sees Mourinho return to the scene of his first major trophy in football - the UEFA Cup with Porto in 2003 - but he is expecting a difficult clash against the La Liga outfit.
"I normally say that Champions League dreams start around the quarter-finals and not yet in the last 16. The last 16 still looks a long way to go. When a team reaches the quarter-finals, then I think is the moment where even the teams that are not favourites, which is our case, realise anything is possible," he told reporters at his pre-match press conference.
"But I think for the moment we just have to focus on a very difficult opponent, and in the first match of these two knockout games, a match that doesn't decide anything is very important. Any team that reach the quarter-finals has a chance. I never thought I was going to win it with Inter or Porto, it's when you reach the quarter-finals that you think something can happen.
"The dynamic can change, the normal tendencies of some clubs are more ready to win it, but when you reach the quarter-finals is when any team can feel anything can happen. This step of going from 16 to eight teams is a very important step. The UEFA Cup in Seville in 2003 meant a lot because was the first time I was playing European competitions with a very young, inexperienced team. For us to win that final meant a lot.
"If my memory is okay I think I had big victories here against Sevilla [with Real Madrid] but I also lost and, honestly, I'm not the kind of guy to think what has influence. I just think that tomorrow and in a few weeks at Old Trafford the two teams are very balanced. I would say the same chances for both, but we want to try and go with everything and we are confident over two legs we can do it.
"I think the game will be very competitive. They can be nice and say we are favourites but that means absolutely nothing. They have good players, a good team and a good mentality for knockout matches. Sevilla is a team of cups – the Copa del Rey and Europa League – and now they have the chance to play in the biggest competition of all so the motivation is even bigger."