Mourinho has given up on United's hopes of securing Champions League qualification via the league and fielded a weakened team in last Sunday's 2-0 defeat at Arsenal.
United are 1-0 up ahead of the home leg of their Europa League semi-final against Celta Vigo on Thursday and with victory in the tournament yielding a Champions League slot, Mourinho says his choices were entirely rational.
"The situation is simple. Seventeen matches in seven weeks with 16 players is impossible. It was not a gamble. It was a simple decision," he told reporters at Old Trafford.
"It was a decision based on common sense. Seventeen matches in seven weeks, April and May. Seventeen matches with 16 players is completely impossible.
"We lost four players in one week, when we lost (Chris) Smalling and (Phil) Jones in the (England) national team and (Marcos) Rojo and Zlatan (Ibrahimovic) against Anderlecht (in the previous round).
"After that we lost boys that could be alternatives: Ashley Young, Luke Shaw, Timothy Fosu-Mensah. When we lost these players in a period of 17 matches in seven weeks, it was the impossible job.
"It was not a gamble, just a consequence of our situation."
Mourinho has already led United to victory in the League Cup, but they lie four points off the Champions League places with three matches of the Premier League season remaining.
More accustomed to competing for Champions League titles, United are bidding to reach the final of Europe's second-tier competition for the first time in their history.
Spanish side Celta have never reached a continental final of any stripe, but Mourinho says there will be no difference between the teams when it comes to their will to win.
"In terms of motivation we are even," said the Portuguese, who led Porto to glory in the UEFA Cup –- as the Europa League was formerly known -– in 2003.
"For Celta, in their words it's the most important match of their history. My feeling is also the most important match of our history. It doesn't matter what happened before, how big the matches before were.
"What matters is the next one and the next one is tomorrow. I don't think Celta want it more than us. So in this aspect I don't think there will be a difference between the teams."
Mourinho revealed United will be without Rojo, Shaw, Young, Fosu-Mensah and Ibrahimovic for the rest of the season, but he reported no new injury problems
Celta have scored in all six of their Europa League away games this season and with United's lead so slender, Mourinho challenged the club's supporters to provide a fitting atmosphere for the occasion.
"I see a difference between matches. I don't think it's consistent, the atmosphere, the enthusiasm," he said.
"For example, the match against Chelsea (which United won 2-0), I could feel they (the fans) wanted to play. They played from the first minute until the last minute. It was really a very strong Old Trafford.
"We had other matches, for example against Anderlecht, where the stadium was not warm enough to make us feel that was a very important match for us.
"And it was, because it was a quarter-final second leg. So hopefully tomorrow they have this feeling it's a semi-final second leg and more important than a quarter-final second leg. So we have to fight hard tomorrow."