Sir Alex Ferguson has told club officials the 24-year-old will not be fit enough to make the trip after being withdrawn with an ankle injury against Bolton on Sunday.
There has been no indication whether Rooney's absence will be any longer, which would threaten his participation in Saturday's Barclays Premier League encounter with Sunderland at the Stadium of Light, plus England's Euro 2012 qualifier with Montenegro on October 12.
Crocked: Rooney will be missing when United take on Valencia on Wednesday
While Ferguson's assistant Mike Phelan revealed Rooney is still struggling with a niggling ankle injury, some may feel it is a good time for Rooney to have a break.
On ESPN yesterday, Kevin Keegan voiced his concern for the striker, who has scored only one goal for United this season, and that came from the penalty spot.
The former England manager, arguably the first superstar English player to attract the modern media spotlight, was asked if Rooney's off-the-field problems were beginning to take their toll.
Keegan did not pull his punches, blaming Rooney for courting publicity and selling the exclusive rights to his wedding, for areported £2.5million, to a celebrity magazine.
'You can't have all the contracts, you can't sell your wedding to magazines and things like this and suddenly say, "That's the tap I want to turn on, but we want to turn the other one off",' said Keegan.
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'It's just one tap and I know, from when I played, that if you are advertising boots and all these things, you have to go and make appearances. You aregoing to appear in the paper.
'But the one thing I would say is keep your home and your family out of it and just take your endorsements if that's what you want to do.
'Youcan't then turn around and say there's too much paparazzi around or there is too much publicity. One minute you are courting it, the next minute you're saying "I don't want this".'
Although the furore over his private life has hardly helped, Rooney was so ineffective against Bolton that purely on form grounds Ferguson might have looked at a combination of Dimitar Berbatov and Michael Owen against Valencia anyway.
Now Rooney can have a couple of days away from the glare of publicity and try to get himself into the right frame of mind for when he next plays.
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