Two goals apiece from Robin van Persie and Javier Hernandez were more than enough for United, who restricted Wigan to very few chances, only a disallowed goal from Arouna Kone coming close to denying them a clean sheet.
And Martinez felt a fourth game inside two weeks had proved too much for his squad, which has been badly hit by injuries recently.
The Spaniard said: "I did feel that we started well, and in many aspects of our performance we were trying to do all the good things we know we can do, but I did feel today was a game too many.
"I thought it was very frustrating for our players. It's been a really busy period and we haven't been able to share the efforts between the squad because we had so many injuries and players missing.
"Today, you look at the opposition and they've been able to make five or six changes from Saturday - I think that paid off for them.
"When you play in these sorts of games you need to be full of energy to be able to react fully in the box, to have that intensity in your defensive play.
"Unfortunately when you look at the goals, it wasn't like they opened us up, it was just second phases at set-pieces. Once the first goal went in, and then the second, it became much, much harder.
"I was very pleased with the mentality and the personality we've shown as it was a difficult performance for us, but four games in 10 or 11 days is a little bit unfair and probably too much of an ask for us facing the leaders."