The bizarre decision to call up Marouane Fellaini for only his fifth start of the season and first since November ahead of Paul Pogba backfired on Tuesday as they were dumped out by Sevilla.
A late double from Wissam Ben Yedder made the difference for the visitors, with Romelu Lukaku's late goal scant consolation after an abject display.
But the Special One preferred to look back on previous United defeats at his hands rather than dwell on this last-16 failure.
"It's not the end of the world. I sit in this chair twice in the Champions League and I knock out Man Utd at home, at Old Trafford," the Man United boss told reporters.
"I sit in this chair with Porto - Man Utd out - I sit in this chair with Real Madrid - Man Utd out... So I don't think it's something new for the club. Of course, being Manchester United manager and losing a Champions League tie at home is a delusion obviously."
Mourinho added to BT Sports: "I think the first goal was always going to be important, not just because of the first leg result but also the profile of the match.
"We tried to be aggressive and intense from the first minute. We didn't score and Sevilla progressively kept the ball, and they controlled the game well.
"We had good chances to score, but they scored one goal and from that moment everything became much more emotional. The second goal made it impossible.
"We had good periods, we didn't have great control over the game, but I can't say there was anything wrong with my players and their intention to play.
"That's football, we lost, but tomorrow is another day and Saturday is another match.
"I'm pleased the players aren't hiding their sadness, but we have no time for drama."