Roberto Mancini's captain walked out of the huge clash in the 20th minute with a suspected groin injury, as Wayne Rooney put the visitors two goals up before half-time
The City captain signalled to the bench that he would not be able to continue in the match with the Premier League champions 1-0 down to their rivals at the time thanks to a Wayne Rooney strike.
The defender has struggled with his fitness in recent months, and was forced to pass a fitness test before their 0-0 draw away to Chelsea.
The Belgian left the pitch looking frustrated and disappointed, with United doubling their lead only minutes later as Kolo Toure replaced the centre-back, with Joleon Lescott left on the bench.
Kompany went straight down the tunnel after leaving the pitch to receive further treatment from the City medical team. The reigning champions will want their captain back with a difficult trip to Newcastle up next in the league.