Mourinho was forced to start the Belgian after Paul Pogba failed to recover from injury in time for Sunday's derby at the Etihad.
Romelu Lukaku had pulled one back for United from the penalty spot but the visitors were comprehensively outplayed.
"He was not ready to play for 90 minutes. I can imagine when it was 2-1 to bring a fresh Fellaini, I think they would be in big, big trouble," he complained.
Mourinho also insisted his side had not played badly despite the scoreline.
"I think it is not a bad performance at all," he added. "It was a performance with mistakes and we paid for it. All three goals are our mistakes. Against a team like City, if you make mistakes you will get punished.
"The first goal is a bad one to concede and the second one is even worse. The third goal kills everything.
"We cannot lose the ball the way we did. It is not about David de Gea, it is about the way we lost the ball.
"We had two matches away [Juventus and then City], it is not the physical effort but the mental pressure. I think some of the boys felt it a little bit.
"Everybody has to agree. It is one thing to go to Juventus and play against one of the best teams in the world for 90 minutes.
"Another thing to beat Shakhtar Donetsk at home 6-0 and be very relaxed. We arrive in different circumstances."