The City skipper has suffered a succession of injuries in his time at the Etihad and made his first start of the season against Southampton in their 1-1 draw at the weekend.
The Belgian made his second start within four days against United on Wednesday, but could only last 45 minutes due to fatigue.
"He told us he is tired and was not ready to play the second half," said Guardiola.
"The important thing is he is not injured - that is a good step".
Before last weekend, the last start Kompany made for the Citizens was in the Champions League semi-finals in May.