The manager claimed last week that the 'exhausting' focus on Rooney was becoming an issue for the player.
Rooney, who watched the final 30 minutes of Sunday's 2-2 draw at Bolton with an ice pack on his left ankle, remained in Manchester while his team-mates flew to Spain for today's Champions League Group C encounter with La Liga leaders Valencia.
He was joined in Manchester United's treatment room by Ryan Giggs (hamstring) and Paul Scholes (calf) as Ferguson prepared for the fixture without three of his more seasoned European performers.
Continuing doubts over Rio Ferdinand's form and fitness following his knee ligament injury have also clouded the 31 year-old's prospects of starting in the Mestalla which, in turn, threaten his prospects of a return for England.
United are understood to be targeting the Old Trafford fixture against West Bromwich Albion on Oct 16 as the earliest opportunity to call on Rooney's services again, ruling him out of Saturday's trip to Sunderland.
Ferguson said: 'I think Wayne will be two to three weeks. In fairness, he's a strong lad and he has recovered from injures in the past.'
When pressed as to the full extent of Rooney's injury, Ferguson refused to go into further detail. He said: 'It's an ankle injury. What do you want me to say? Do you want me to describe every ligament? Christ!'
Having scored five goals in seven Champions League appearances last season, Rooney's absence is a big loss for United, despite his faltering form this campaign.
Little has gone right for the player since he suffered an injury to his right ankle in the final minute of the quarter-final defeat at Bayern Munich on March 30. His latest injury problem stems from a twisted ankle suffered in the 0-0 draw against Rangers earlier this month.
But with the seen-it, done-it experience of Giggs and Scholes also unavailable to Ferguson against Valencia, the manager concedes that the timing of Rooney's injury is hardly opportune.
He said: 'You don't want to lose your best players. The problem is that these small injuries sometimes just need to get better — particularly Scholes. If he travels and spends time on a plane, stiffness sets in and it doesn't get any better. He should be better in 10 days, but it was a big decision to leave Scholes behind. With Giggs and Wayne, there was absolutely no choice.
'We're going to have to adjust the team now.'
Deprived of his leading striker and without the combined Champions League experience of Giggs, Scholes and Gary Neville, Ferguson's plans for team adjustment are further compromised by Ferdinand's fitness.
Ferdinand, still officially the England captain despite his injury-ravaged past four months, has been overlooked in favour of Jonny Evans for Premier League fixtures since returning to fitness.
Chris Smalling's emergence has left Ferguson considering the £12 million summer signing ahead of Ferdinand as partner for Nemanja Vidic in Spain.
Troubled throughout last season by a persistent back problem, Ferdinand spent much of the two-hour flight to Valencia on his feet and he left the plane carrying a booster seat.
And having left Ferdinand out of his 18-man squad at Bolton Sunday, Ferguson admits he has yet to decide whether to recall the former Leeds defender tonight.
He said: 'Rio's had plenty of training and a couple of reserve games. He had a game against Rangers, but I think he probably needs another game or two.
'It's a decision I will take on Wednesday. The important thing is that he's coming back.'
With Valencia unbeaten this season and United having won just once in 18 games against Spanish opponents in Spain — 2-0 against Deportivo La Coruña in 2002 — Ferguson acknowledges this game will be his team's toughest of the group.
'Valencia's record in the competition guarantees that they'll be favourites with us to qualify. They are playing very, very well.'