But when they realise Italian Daniele Orsato will be the referee in charge of proceedings at the Theatre of Dreams, you could forgive them for going into the match with a bit of caution.
His name might not mean much to you but Orsato has overseen two big shocks involving United in the Champions League.
Just last season, he was the man in the middle when Swiss champions Basel ran out 1-0 winners in the group stage thanks to a last-gasp Michael Lang goal at St Jakob-Park.
Mourinho’s side needed only a point to secure their place in the knockout stage and should have been five or six in front at half-time.
Instead, they were made to rue their luck as Lang turned home from close range with just a minute on the clock.
The result counted for little in the end as other results meant United simply needed to avoid a seven-goal defeat to CSKA Moscow in their next group game to progress and they beat the Russians 2-1 secure top spot in the group.
But that was the second time Orsato had overseen a shock loss in three years. If we rewind to December 2012 for you might recall a match that ended in almost total embarrassment for United.
While Sir Alex Ferguson’s passage to the last 16 was already secured, a home tie against Romanian minnows CFR Cluj should have been a formality.
Ferguson even named a strong side that night, with the likes of Wayne Rooney, Ryan Giggs, David de Gea and Javier Hernandez all included from the start.
What transpired was a wretched display that led to United’s first home defeat in the Champions League for a whopping three years as they were accused of being distracted by a top-of-the-table Premier League clash with Manchester City four days later.
In their defence, United went on to win the Manchester derby 3-2 and were eventually crowned as champions after finishing 11 points above second-placed City.
Elsewhere, Orsato has proved to be a bad omen for Chelsea, the Italian overseeing their surprise 1-1 draw at Maribor in the Champions League group stage in 2014.
The Italian also took charge of Mourinho’s first Champions League game after returning for a second spell at the club in 2013 – and his happy reunion was short-lived after they lost 2-1 to Basel at Stamford Bridge.
Even Pep Guardiola‘s Man City are not immune to the curse of Orsato, who was in control for their 2-1 home defeat to Lyon in this seasonn’s group stage.
But if United fans are now starting to panic, they might take some encouragement from Liverpool‘s 5-0 win at Porto in the last 16 last term.
And Orsato was the official for what might be Leicester’s creates ever European night as they overturned a 2-1 first-leg deficit against Sevilla in the last 16 of the 2016-17 Champions League by winning 2-0 at the King Power Stadium.
DANIELE ORSATO’S CHAMPIONS LEAGUE GAMES INVOLVING ENGLISH CLUBS
Sep 19, 2018: Man City 1 Lyon 2 Champions League group stage
Feb 14, 2018: Porto 0 Liverpool 5 Champions League last 16
Nov 22, 2017: Basel 1 Man Utd 0 Champions League group
Mar 14, 2017: Leicester 2 Sevilla 0 Champions League last 16
Nov 5 , 2014: Maribor 1 Chelsea 1 Champions League group
Sep 18, 2013: Chelsea 1 Basel 2 Champions League group
Dec 5, 2012: Man Utd 0 Cluj 1 Champions League group