Mourinho made nine changes to the lineup from Monday's 1-0 Premier League win at Burnley but Spurs fell behind inside 30 minutes after an error from defender Ben Davies allowed Antwerp forward Lior Refaelov to score from close range.
Dele Alli, Steven Bergwijn, Giovani lo Celso and Carlos Vinicius were all replaced at halftime but Spurs were unable to get back on level terms. It was their first defeat since losing 1-0 to Everton on the Premier League's opening weekend in September.
"I would like to have made 11 changes at halftime," Mourinho told reporters. "I didn't make five as I was afraid of a long 45 minutes.
"I always like to think the players deserve an opportunity. We have a big squad with lots of good players," he added.
"It's my responsibility to give them opportunities but it's also their opportunity to catch the chance with both hands and ask for more.
"Tonight shows my future choices are going to be very easy." (Reporting by Hardik Vyas in Bengaluru; Editing by Peter Rutherford )
