It certainly would be a half that either side would want to forget with Joaquín Correa glancing one over in the opening minutes, United picked up the pace towards the end but the chance from Marouane Fellaini proved to be their only smell of an opening goal.
Things picked up in the second period with Jesse Lingard going close but a quick-fire brace from Wissam Ben Yedder gave United an seemingly impossible mountain to climb, Romleu Lukaku managed to get one back to give the Old Trafford a glimmer of hope but the damage had been done.
Nothing to write home about
The Red Devils will have felt lucky to have come back from Spain with the scoreline intact mainly down to David De Gea and should have been buoyed by their performance at the weekend against bitter rivals Liverpool but both sides despite the weight of fixture fell flat throughout most of the first-half.
Sevilla looked to test the waters early on as Correa did well to attack Éver Banega's corner, he was gifted the chance by Nemanja Matić who left him in acres of space but it glanced over De Gea's crossbar.
José Mourinho's side grew more and more into the clash as the minutes clocked with their chance arriving eight minutes before the break, United caught the Spaniards napping as Alexis Sánchez fed the ball back to Fellaini who forced Sergio Rico to beat the ball away from the difficult angle.
Looking to make a good start
United carried that form into the beginning of the second period as Lukaku did well to get to battle for the ball and give it to Lingard, it was again from an acute angle which Rico once again did well to tip away.
Suffering a deadly double blow
That would come back to haunt United in a big way as Sevilla shocked The Theatre of Dreams with the opening goal, Pablo Sarabia did well to look up and find Ben Yedder who made space with his first touch to get away from Eric Bailly and fired into the bottom corner.
He was there once again only three minutes later and there was an element luck to it all, Correa's cross found the head of Ben Yedder whose header looked to be dealt with by De Gea but the touch off the crossbar just took it over the line.
Surely not another comeback?
Though the odds seemed very much stacked in their favour United fans will have been buoyed by the win over Crystal Palace, and the glimmer of hope returned with Lukaku bringing one back. It was simple enough as Marcus Rashford whipped in the corner, and the Belgian rose highest to slam past Rico.
It could have gone from bad to worse right at the death as Ben Yedder looked nailed on for the hat-trick, with the one-on-one looking destined for a third but De Gea did brilliantly with the save.