Michael Carrick has been sidelined for the next four to six weeks after hobbling out of Saturday's 2-1 defeat to Liverpool with a broken bone in his foot.
The Manchester United midfielder missed training on Tuesday ahead of the club's UEFA Champions League opener against Villarreal the following evening, prompting speculation he had picked up a serious injury.
Those suspicions have now been confirmed as United brace themselves to be without the talented schemer for up to six weeks.
Carrick will miss Wednesday's game with Villarreal and is now a major doubt for forthcoming European clashes with Aalborg and Celtic.
In Carrick's absence, when coupled with Paul Scholes' suspension, United boss Sir Alex Ferguson will likely pair Owen Hargreaves with Anderson against Villarreal, although Darren Fletcher will also come into contention.
Carrick will be doubly disappointed with this latest setback, given the Liverpool game marked his first appearance since he picked up an ankle injury in United's season opener against Newcastle.
Ferguson admits Carrick's injury is not his only concern as Dimitar Berbatov and Wes Brown are also receiving treatment on knocks they picked up in the Liverpool game.
"We have some injury problems for tomorrow," conceded Ferguson.
"Michael Carrick, as you know, it's not worked out for us. He came off on Saturday and he's got a crack in his foot.
"It was diagnosed on Sunday afternoon and he'll be out for four to six weeks, which is not good news.
"Berbatov is very doubtful following his knee injury in Saturday's game. There's one or two other bumps and bruises. Wes Brown got a knee injury, hopefully he'll be okay tomorrow.
"Berbatov came off and went back on again in the game. There is swelling on the knee but we're working on that. We'll see.
"We've a good strong squad so we should be okay for what is an important game."
It was not solely doom and gloom in Manchester though, as Cristiano Ronaldo is primed for his return following ankle surgery over the summer.
Ronaldo's name rarely escaped from the back pages in the close-season, as Real Madrid's pursuit of his signature became the most protracted transfer story of the summer.
It will be interesting, therefore, to see what kind of reception he receives from the Old Trafford faithful, if as expected he makes an appearance off the substitutes' bench.
"He'll certainly be involved. Whether we start him or not, regardless of other players, is not a major decision. I think he'll start on the bench," concluded Ferguson.