But with a four-point lead at the top and a game in hand, United remain firm favourites - and Charlton believes the shock loss can spur them on.
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Talking to the BBC Charlton said: "I think there was just a little bit of stress, because we kept on winning matches. It helps to maybe turn the gas down a little bit, and a lot of pressure's maybe eased. I'm hoping we're going to do better because of this result.
"It wasn't a result anybody at Manchester United could be proud of, but you have to say Liverpool played really well and deserved to win."
It was United's heaviest home defeat since losing by the same scoreline to QPR in 1992, but Charlton has no doubt manager Sir Alex Ferguson will soon pick the side up.
"He will make sure they get their confidence back," he added.
"It's a bit of a blow - to lose four goals at home hasn't been done for so many years. There's bit of pride been hurt there, but I don't think he'll have to work too hard to rejuvenate them.
"But work he will. Getting to the end of the season, all matches are important. When the next one comes along next week I'm sure he'll be ready for it."
United remain on course to win a remarkable quintuple this season. The Club World Cup and Carling Cup are already in the bag - while they are also through to the last eight of the Champions League and semi-finals of the FA Cup.
Charlton, who won the European Cup with United in 1968, believes the current squad could go on to prove Old Trafford's greatest ever.
He said: "It is a very good squad with a lot of good players. I think maybe if they win the Champions League you could say that is maybe the best squad that's been here."
On the possibility of winning five trophies, he added: "It would be absolutely sensational and if any club were ever able to do it it would be the greatest achievement any club has ever had. But we don't have any targets other than the next match."