Fulham capitalised with goals from Danny Murphy, Bobby Zamora and Damien Duff to complete their second home triumph over United in as many meetings.
The champions have already suffered one more defeat than they did in capturing a third successive Premier League title last season.
"There was a fragility at the back and we couldn't do anything about that," said Ferguson. "You have to have sympathy for the players in that respect.
"It's difficult to play midfielders at centre-back, and Ritchie de Laet is only 21 years of age. He's not got the experience yet needed for these type of matches.
"It was a terribly soft goal for the first one, and that gave them the platform to build on.
"To concede 20 seconds into the second half killed the game. We didn't anticipate that. And it was a poor decision by the referee for the third goal.
"We couldn't get behind Fulham at all and their defence is very well organised. It was a difficult day for us.
"But the quality of the football wasn't as good as it normally is. The fragile nature of the players at the back, with midfielders playing in defence, has left them feeling sorry for themselves a bit."
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