Saturday's 1-0 win over Tottenham was the second successive top-flight win for Wolves - the first time the club have achieved that in 26 years - and lifted them out of the relegation zone, although they are now back in the bottom three after losing to Sir Alex Ferguson's side.
But McCarthy responded to the victories by keeping faith only with keeper Marcus Hahnemann against United, explaining afterwards that the physical exertions of the players at White Hart Lane ensured they needed a rest.
The second string went on to lose comfortably, leaving many Wolves fans bemused and frustrated, but chief executive Jez Moxey tried to justify his manager's selection.
He told BBC Sport: "Of course we were all surprised by Mick's team selection but it is his prerogative to pick whatever team he sees fit for any particular game.
"He is very cognisant of what the fans want and I think what they want most is to stay in the Premier League. Mick is picking a team for each individual match that will give us the best chance to do that.
"You have to remember that 10 of our first-team squad have already had serious operations and/or injuries this season already and Mick has to bear that in mind.
I thought there was something to be gained from that match on Tuesday
North West Wolves fan chief Arthur Williams
"As he has said publicly, he can understand the fans not being happy but it is down to him to make decisions in the best interests of the club and that is what he did."
However, Williams, head of the North West Wolves supporters branch, countered to BBC Sport: "Listening to Mick's reasoning, you can understand it but then he confounded it by saying we've got some big games coming up. Well surely last night was a big game?"
"Coming as it was on the back of a win at Tottenham, I thought there was something to be gained from that match on Tuesday.
"It's well catalogued that United haven't the best of defences at the moment, with injuries and so on, and I just thought with the likes of the players that were missing we just might have pressed on and got something out of it.
"Wolves sold out their allocation, paid £42 each, plus the time and cost of travelling, and my first reaction when I saw 10 changes and players playing out of position was, I thought, grossly disrespectful."
Williams ruled out fans seeking a refund though and admitted that if McCarthy's side go on to beat relegation rivals Burnley on Sunday, all would be forgotten.
McCarthy bullish over team selection
"I know it's easy as a fan to criticise and it's down to the manager at the end of the day to say he knows best," he stated. "I can't complain too much because his knowledge of being best has been pretty good over the last couple of years or so.
"That said, I hope he doesn't adopt this attitude in other matches. I'd rather he strengthened the squad in January and did things that way.
"But come Sunday the ground will be full again, the fans will be behind Mick McCarthy and the team and if we beat Burnley all this will be forgotten."
Those sentiments were echoed by Wolves legend Steve Bull, who told BBC Radio 5 Live: "I was disappointed when I saw the team, just like the other 3,000 Wolves fans there.
"But deep down I think realism comes to mind where you've got Burnley on Saturday so you'd rather field a very strong side there.
"Realistically, we got three points at Spurs where we didn't expect three points and Mick's come away probably thinking don't bite off more than you can chew. I think he's thinking Man Utd are going to walk all over us and we'd be lucky to get a draw never mind a win, so why not.
"As fans you have to bite your lip some days. You're going to get good games with a full side some days and some days you're not."
And A Load of Old Bull Fanzine editor Charles Ross added: "I can understand fans being disappointed but in many ways it is representative of the unlevel nature of the Premier League.
"The gulf between the haves and have nots is so huge that Wolves absolutely must do whatever it takes to try to stay in the division this year.
"Survival is everything, it is absolutely crucial. Had fans been offered three points from matches away at Tottenham and Manchester United, they would have bitten your arm off whichever way it had come about.
"I can understand entirely why he took those decisions. Mick will be judged over 38 games and based on the resources that he has available. I certainly don't think last night's selection and result is cause for a hanging party."
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