The midfielder is sidelined with the hamstring injury he suffered against Wolverhampton Wanderers on Saturday - and Ryan Giggs is also ruled out of Wednesday's Manchester derby.
Making his first senior Manchester United start since September 2008, Hargreaves lasted just six minutes before he pulled up indicating he had suffered a problem and had to be replaced by Bebe.
Now Ferguson has revealed the 29-year-old will be out of action until the middle of next month, although it is possible Hargreaves could play some part in the Christmas programme.
TOO MUCH
"We were at the stage where we knew Owen's knee was okay," Ferguson said.
"His training performances for eight or nine days previously had been terrific.
"He had done really well, which is why we took the chance.
"But maybe the tension in the build-up for the lad was too much and he suffered because of it."
As soon as Hargreaves came off on Saturday, Ferguson knew he would play no part against City.
But the loss of Giggs is a major blow.
The veteran Welshman was hoping to make a record 34th derby appearance at Eastlands but after feeling the hamstring injury that has kept him on the sidelines for all but one of United's last nine matches in a session just prior to Saturday's win over Wolves, Ferguson has reluctantly ruled Giggs out of his plans.
"Ryan is out," said the Scot.
The news on Nani was not much better either.
UNTESTED MEMBERS
Although there is an outside chance the Portugal winger may recover from the groin injury he suffered in last week's Champions League triumph over Bursaspor, Ferguson is dubious about Nani's prospects of facing City.
"Nani is doubtful," said Ferguson.
"At this stage it doesn't look as if he will make it. It is not a great position for us to be in. We are counting heads at the moment."
United's problems are not made any easier by a virus that has swept their Carrington HQ since the return from Turkey, with Patrice Evra, Nemanja Vidic, Dimitar Berbatov and Paul Scholes all believed to be amongst the victims.
It means Ferguson might again be reliant on some of the untested members of his squad for one of the biggest nights of the season.
"There is nothing more satisfying than winning a derby game," he said. "It doesn't matter what year it is or when it is."