Manchester City manager Manuel Pellegrini confirmed Vincent Kompany will miss a minimum of a month of action after sustaining a fresh calf injury against Dynamo Kiev in the Champions League on Tuesday.
Kompany appeared to be over the worst of the issue that has blighted his campaign after playing in City's past six matches.
However, the issue reared its ugly head again for the Belgium centre-back when he limped off early in City's 0-0 draw against Kiev - a result that secured their place in the Champions League quarter-finals for the first time thanks to a 3-1 aggregate win.
Pellegrini confirmed at his post-match news conference that Kompany will miss a "minimum of a month", meaning he is out for a crucial period of City's campaign.
"Vincent has a problem in his calf, the same as before. We'll know maybe tomorrow or the day after tomorrow how important it is, but always muscle injuries are at least one month," he said.
"It's difficult in this moment for me to say [if he will play again this season]. It is a problem in his calf and we are in the middle of March so I would say at least three quarters of the [rest of the] season he will not play."
Kompany is definitely out of Sunday's derby against Manchester United in what is surely a must-win game for City's Premier League title hopes, as well as next month's Champions League quarters.
He also sits out league matches against AFC Bournemouth and West Brom, while his availability against Chelsea on April 16 is in doubt.
Pellegrini added on BT Sport: "Unfortunately for Kompany he has again a calf problem. We'll see how bad it is tomorrow [Wednesday].
"It's difficult for him. He came back very well and played six games in a row, unfortunately he couldn't continue. We'll see how bad it is."
City's worries worsened midway through the first half at the Etihad Stadium against Kiev when Kompany's centre-back partner Nicolas Otamendi also hobbled off.
But Pellegrini is hopeful his injury is not too severe, adding: "Nicolas Otamendi has had a kick and hopefully can recover in the next couple of days."
