(CNN) -- Wayne Rooney will be sidelined for up to three weeks, missing crucial games for club side Manchester United and England.
United manager Alex Ferguson confirmed Tuesday night that the striker's ankle problem had flared up again.
He was substituted in the 2-2 Premier League draw at Bolton on Sunday and did not travel with the United squad for their tough Champions League tie in Valencia on Wednesday night.
The injury update from Ferguson means Rooney will miss the Premier League game at Sunderland on Saturday and also England's Euro 2012 qualifier against Montenegro on October 12.
Ferguson also revealed that veteran midfielder Paul Scholes will be out for 10 days with a calf problem.
"It will be two to three weeks," said Ferguson. "But it depends because Wayne has done quite well with his recovery from injury in the past."
Rooney, who has found himself the subject of newspaper revelations about his private life, has struggled for form since the World Cup. He was even left out of the side when United faced former club Everton recently.
His manager believes this can be attributed to Rooney's personal problems.
"The boy is starting to realize probably, finally, without any question, what kind of focus is on him as a human being," Ferguson told Italian newspaper Gazetta dello Sport recently.
"For a young person, that is not what you want. You want to play and enjoy your football without that attention. That can be quite exhausting."
Ryan Giggs is also missing the trip to the Mestalla Stadium, with the Welshman suffering from a hamstring injury.
Despite the absence of three key players, the Old Trafford side will be keen to put the disappointment of their goalless draw with Scottish Champions Rangers in the opening match behind them.
Currently top of La Liga, Valencia also head Group C of the European competition after beating Turkish side Bursaspor 4-0 in their opening game.