They have enhanced their position with victories over Bolton and Spurs - the first time they have secured successive top-flight wins in 26 years - but McCarthy felt the best option against Manchester United was to rest many of his regular players.
"We could have got beaten whatever team I put out and I might have lost somebody with a hamstring or calf strain because they were all struggling after beating Spurs," stated McCarthy.
"It's my decision and the responsibility lies with me."
Despite being without Stephen Ward, Jody Craddock and Richard Stearman, the visitors defended well at Old Trafford before going down to a Wayne Rooney penalty, a Nemanja Vidic header just before the break and an Antonio Valencia half-volley.
Yet many Wolves fans were left seething at McCarthy's decision to field a weakened team.
They vented their frustration by chanting "we want our money back", "where is our first team" and "£40 to watch the reserves".
But McCarthy insisted his selection was fully justified.
"I can understand the supporters' reaction but at the end of the season I will be judged on whether Wolves have stayed in the Premier League or not," he said.
"It was a hugely difficult game against the champions and I thought we did OK. None of them let me down.
I'm not bothered about the reaction from anybody else... I make decisions for what I think is the good of my players and the good of the club
"We have 21 fit players and three players facing operations. The Spurs game really took it out of them. The 10% chance of injury increases to 30-40% if you have another game like that.
"I'm not prepared to get injuries before the weekend. You can't argue with the scoreline with United but there are some plusses," he added, highlighting "outstanding" performances by on-loan Chelsea defender Michael Mancienne and midfielder Andrew Surman.
Wolves could be punished by the Premier League, whose regulations insist clubs field their strongest team in every top-flight contest.
However, even though such action is unlikely, Chelsea may feel aggrieved after Manchester United's comfortable win pulled them level on points with the Blues at the top of the table.
"I'm not bothered about the reaction from anybody else," insisted McCarthy. "When I go into their office at Chelsea or Arsenal manager Arsene Wenger comes into my office at home, there was no sympathy for me, they had just turned round and slapped me.
Phelan relieved United back on track
"I make decisions for what I think is the good of my players and the good of the club. I knew those questions would be asked of my decisions but what I haven't got is any more injuries."
United manager Sir Alex Ferguson wasn't surprised that Wolves made so many changes, praising the visitors for "putting up a good show".
In his 900th league game in charge, Ferguson was pleased with the victory after the surprise defeat by Aston Villa on Saturday.
However, earning three points and drawing level with leaders Chelsea on points was tainted by a calf injury to Nemanja Vidic, with United hoping he will be fit for Saturday's game at Fulham.
"He came off with a slight problem and we just hope he can recover in time," added Ferguson.
"Wolves made it a difficult night for us. They pressed the ball, tackled everywhere and put up a good show, considering they had most of their second string, which wasn't surprising because they have got Burnley on Sunday.
"We took a long time to get our game going and the changes we are making are not giving us consistency of performance but once we got the first goal it was comfortable enough."
With midfielders Michael Carrick and Darren Fletcher likely to carry on deputising at the back, left-back Patrice Evra is one of the few fit defenders.
"I go to church and pray every day the centre-backs will recover!" joked the Frenchman.
"After the defeat by Villa, it was important we reacted well. We have a tough game against Fulham now and it is important to win that and every game before the end of December because now the title race is starting."
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