After all, having failed to find the net in the first meeting at the Ramón Sánchez Pizjuan three weeks ago, returning to Manchester with a credible 0-0 but without a precious away goal, conceding against the Spanish side at Old Trafford could have dire consequences.
But Mourinho should resist the urge have his men sit back and bide their time, taking a reactive, rather than proactive, approach. This Sevilla side are there for the taking, and it's time for United to shake off the shackles and stamp their authority.
In front of a baying home crowd, on a European night with the eyes of the world watching on, this is a chance for Mourinho and United to quieten some of the doubters that remain, despite positive recent results.
United have won four of their last five fixtures since their unexpected defeat at the hands of Newcastle United in February, with the draw away to Sevilla the only blot on their copybook of late.
However, while nine Premier League points from a possible nine and a place in the FA Cup quarter-finals is as much as could have been hoped for, they are yet to produce a truly comprehensive performance in this period.
Of course, in the visits of Chelsea and Liverpool to Old Trafford, the result was paramount, and a 2-1 victory was scored on each occasion. And while United deserve credit for taking all six points from their top-four-battling rivals, they were outshot and saw less of the ball in both games – these were classic Mourinho performances, and there's nothing wrong with that.
The dramatic 3-2 win against Crystal Palace at Selhurst Park last week, in which the Red Devils overturned an two-goal half-time deficit to snatch a win thanks to a stunning Nemanja Matić trike in stoppage time, left the United support buoyant.
But for the first 45 minutes, the 20-time champions were atrocious, thoroughly outplayed by their struggling opponents and looking a far cry from the Premier League's second-best side.
Against Sevilla, United have the opportunity to put in a dominant 90-minute display, laying down a marker in Europe's premier club competition and producing the kind of performance Mourinho can point to as evidence of the progress he has overseen. And they have the perfect dance partner.
Sevilla has been wholly unimpressive in La Liga this term. They currently sit fifth in the table, but they're closer to Espanyol in 12th than they are to fourth-placed Valencia.
The Andalusians have lost 11 times in the league, own the joint-worst defensive record inside the top nine, and have scored fewer goals than every side in the top half except for over-performing minnows Eibar.
Individually, no Sevilla player has scored more than six league goals this term, nor mustered more than five assists.
This is not, by any stretch of the imagination, a vintage Sevilla side. But the club's name still carries certain credibility, especially in continental competition. While their policy of regular player turnover means few faces remain from their back-to-back-to-back Europa League triumphs of just a few years ago, Sevilla are still a team associated with achievement in Europe.
As such, confidently and comfortably dispatching them would be a feather in United's cap. Paul Pogba is an injury doubt after missing the Liverpool game, but with the likes of Alexis Sánchez, Juan Mata and Marcus Rashford raring to go, the Red Devils have more than enough firepower to put Sevilla to the sword.
What's more, it makes perfect sense for United to strike early and strike often on Tuesday night. The longer the game remains scoreless, the more tension will grow inside Old Trafford, along with Sevilla's self-belief.
Lessons, to that end, can be drawn from United's Europa League victory over Celta Vigo last season, where, but for a shocking miss by former Manchester City striker John Guidetti late on, Mourinho would not have been able to raise three fingers at the end of the season in an effort to claim a dubious treble.
With the Premier League title destined for the blue half of Manchester, and their position in second all but assured by those wins over Chelsea and Liverpool, United can afford to focus their efforts on the Champions League. Dispatching Sevilla in style could turn a few doubters into believers.