But perhaps the thing that will hurt Red Devils supporters the most was the sight - and reaction - of Sir Alex Ferguson watching from the crowd.
The Red Devils played deep in the first half and seemingly waited for opportunities to counter, despite being the home side.
Sevilla were happy to bide their time playing away from home knowing than an away goal counted for much more than a Red Devils strike.
Very little of note occurred in the first half as a result of the stand-off between the two teams, and any time either side attempted to hit the opposition on the break, they did so slowly and lethargically.
Wissam Ben Yedder came on for Sevilla midway through the second half and netted two important away goals, leaving United far too much to do, even with their late Romelu Lukaku consolation.
BT Sport cameras picked out Ferguson in the stands after Yedder hit the back of the net, and he looked nothing short of devastated by the goal.
He also appeared to be pointing out positional errors on the pitch, perhaps considering what he'd have done if he was still boss.
After the game Mourinho defended his reputation, pointing out that he has previously got the better of Ferguson.
"I've sat in this chair twice before in the Champions League, and I knock Man United out at home twice, with Porto - Man United out, and with Real Madrid - Man United out," he said.
"So this is nothing new for this football club. I don't want to make a drama out of it, we don't have time for that.
"We have a match on Saturday, we have no time to be sad for more than 24 hours. And that's football, it's not the end of the world."
Mourinho’s comments have received fierce reaction from the Red Devils faithful, where many of them have gone as far as calling for his sacking. It is just a matter of time for Sir Alex Ferguson to comment about the loss. But one thing could be certainly sure that Mourinho’s comments may not augur well with Manchester United legend.
Mouronho is not new to rubbing shoulders with fans and sports personalities. Such incidences also happened during his stints at Chelsea and Real Madrid.