Pep Guardiola says Vincent Kompany will be out for "weeks" with a knee injury.
Kompany was withdrawn during the first half of Manchester City's 2-1 victory at Crystal Palace on Saturday following a collision with goalkeeper Claudio Bravo.
Guardiola initially feared Kompany had suffered a head injury, but that is not the case.
However, the City boss has revealed that the centre-back has injured his knee, and his "sad" about his latest set-back.
"He's injured," the City boss said ahead of City's Champions League game against Borussia Monchengladbach. "Fortunately there is nothing wrong with the head, but it is his knee. He will be out for weeks."
Kompany did not travel with the rest of the City squad to Germany and is now facing yet another spell on the sidelines.
The Belgian returned to the City line-up on Saturday for the first time since the end of October, having only just returned to the first team after limping out of his first match of the season at the end of September.
Kompany missed the majority of last season with persistent muscle problems and it was put to Guardiola that he may leave the defender out of his Champions League squad for the knock-out stages.
"I think now is not the moment because first we have to qualify, and after that we are going to decide," Guardiola replied.
"We are going to decide in that moment. We are looking for Vincent to stay in the team, because one day it's a muscle problem, the next time it's you know... We are trying to help him to play more often."