Ole Gunnar Solskjaer's Reds come into this game on the back of a 4-0 win over the La Liga side, and could increase that goal margin if they can replicate a similar performance to the one they showed in Italy last week.
Here is what United fans can look out for ahead of the 2nd leg tie at Old Trafford.
Significant team changes?
A 4-0 in Italy has meant the Reds come into this tie with a large goal advantage, which could allow Solskjaer to make significant team changes.
Diallo will be a very interesting watch for United fans if he is chosen to start tonight. The £40million signing has had United fans impatiently waiting for his full United debut since his arrival.
The upcoming weekend sees United travel to Stamford Bridge to face off against Chelsea, meaning Solskjaer could have one eye on that game and may choose to rest key players in Bruno Fernandes, Marcus Rashford and Luke Shaw.
United should wrap up the tie tonight, however, as we've found out in recent European years, anything can happen in Football - an unlikely comeback from the Basque outfit could be possible if the Reds fail to nullify the front three of Mikel Oyarzabal, Alex Isak and Adnan Januzaj.
Can United end their bad streak against Spanish sides in a European game?
If United manage to go through to the Round of 16 they will have ended their run of failing to beat a Spanish side since 2017 - when they beat Celta Vigo in the Semi-final of the Europa League.
The Reds win last week in Turin saw them end a run of nine games without a win against La Liga sides. In that nine-game run, United have failed to beat the likes of Real Madrid, Barcelona, Sevilla and Valencia.
Providing United do not lose by a four-goal margin to the Basque side tonight, they would have finally have broken their bad run of games against Spanish sides in European competitions.