While it has just been decided to eliminate the competition's renowned 'away goal' rule, the Red Devils, led by German interim manager Ralf Rangnick, will be anxious to take a positive result away from the Wanda Metropolitano Stadium.
In spite of the importance of the match, one person who is feeling confident is renowned former manager Sir Alex Ferguson, who, in a recent interview with supporters, made an astonishing prediction on which team would win.
When questioned about his predictions for Wednesday's mega European match, the former Scottish manager responded, "Hopefully [Man United will win]."
"I'll settle for a score of 5-0."
Alphonsus Odumu 5 w
Sir Alex prediction