Chelsea were well beaten at Old Trafford as two goals from Scott McTominay secure a 2-1 win for the hosts.
Robert Sanchez made multiple big saves, including from a Bruno Fernandes penalty kick, allowing Chelsea to equalise just before half-time through Cole Palmer.
But when asked why his team were dominated on Wednesday night, Pochettino suggested Conor Gallagher's first-half red card at the weekend may have played a part but admitted United were the better team.
He said: "It was difficult at the start, they showed massive energy. Maybe we were affected because we played Sunday with one less [player] for 60 minutes with similar players.
"Maybe it was difficult for us to start the game in the way that we wanted. Maybe that was one of the reasons why we didn't start the game well.
"This type of game is difficult to assess because of how [important] one day more was for Manchester [United] to recover and for us to play 60 minutes with one player less. With this situation, we missed a little bit of energy from the beginning."
"My feeling was they were better than us and deserved to win."
Pochettino cut a calmer figure after yet another defeat despite seeing his Chelsea side booed by sections of the away support after such a limp performance.
It was a far cry from the anger he showed after the 4-1 defeat away at Newcastle.
"It's similar to a few weeks ago and months ago; we want to improve the position in the table, of course, but, at the same time, it is a reality that we played well until Newcastle, then well against Brighton and, today, the result is fair," he explained.
"I am not worried because there are too many circumstances. You have to say why we didn't perform.
"We are a project and not going to say what we were saying from the beginning of the season. We knew that with all the players fit, it was going to be difficult.
"Now, with half the squad out, it is hard to increase the level, very, very difficult. It is hard to talk, not fair but that's the reality. We have to improve the players who arrive under massive pressure to perform, and it is about time.
He added: "Now is not the same [feeling as Newcastle] because we miss players. I think we played against Brighton with one player less for 45 minutes. You can see also our bench is young.
"That is not an excuse but if we need to talk, we need to talk with the reality. I am not disappointed because they gave everything.
"Yes, we didn't match the energy and they were more aggressive than us but we were competitive and created chances, maybe enough to draw the game.
"We lost 2-1 and we got nothing so that might be where we get critics and people finding different reasons why we didn't win. But we need to be calm and keep going."