Spurs could be without the talismanic duo of Harry Kane and Son Heung-min for the rest of the season through injury and looked toothless against the Bundesliga contenders.
"We are in a very difficult situation," said Mourinho. "What worries me is this is going to be the situation until the end of the season."
Tottenham captain Hugo Lloris kept his side in the tie with a string of important saves, but he could not prevent Timo Werner from the penalty spot as the German international's 26th goal of the season gave Leipzig a lead to defend on home soil on March 10.
"Over the 90 minutes we deserved the win and could have won by more," said Leipzig boss Julian Nagelsmann.
"It's only the first game today. You have to perform at the same level in both games."