Sir Alex Ferguson has confirmed that Nani will miss the Manchester derby at Eastlands.
The winger missed Saturday's 2-1 home Premier League victory against Wolves with a groin injury and is unlikely to face rivals City on Wednesday night.
The Portugal international picked up the knock in United's Champions League win over Bursaspor in midweek.
Ferguson sent out a depleted side against Wolves due to injury and flu and his understudies had to rely on an injury-time goal from Ji-sung Park to secure a dramatic win.
Wayne Rooney, Dimitar Berbatov, Darron Gibson, Anderson, Michael Owen and Ryan Giggs were all missing at Old Trafford, though Nemanja Vidic and Patrice Evra were required to play.
However, there was some good news for the United boss who expects Berbatov to be back in training on Monday.
The Bulgarian striker was expected to lead the line against Mick McCarthy's men but withdrew after picking up the virus.
He is, however, expected to make his 100th appearance for the club against Roberto Mancini's side on Wednesday.
"This is a busy time for us right up until the new year," noted Ferguson. "We have Manchester City on Wednesday and Chelsea and Arsenal in consecutive weeks.
"Nani won't be fit for Wednesday but I hope Dimitar Berbatov will be in to train on Monday."