The international marquee is yet to make an appearance for his club after picking up a calf injury ahead of the first round of the A-League season.
Head coach John van 't Schip revealed on Sunday that Koren had suffered a setback in training and days later confirmed it could sideline him for up to six weeks.
News of Koren's significant setback comes after City's winless start to the campaign and follows quickly after revelations that Spanish star David Villa - at the club as a guest player from New York City FC - will not complete his maximum 10-game spell in Australia.
The injury to Koren is strangely reminiscent of the fate to befall last season's international marquee, Dutch midfielder Orlando Engelaar, who broke his leg in pre-season and did not make his competitive debut until late January.
Villa, who has scored both of the club's goals this season, is likely to start again when City meet second-placed Melbourne Victory at Etihad Stadium on Saturday.
The outing looks set to be his second last for City, who have needed equalisers from Villa to draw their opening two games.
Kevin Muscat's Victory enter the clash as favourites and are one of the title fancies.
Elsewhere in round three, the team with the only perfect record – Perth Glory – travel to Adelaide on Sunday.
Glory striker Andy Keogh is the league's form player and has already scored four times, including a hat-trick against Brisbane last time out.
Last season's grand finalists – Brisbane and Western Sydney – are the league's only point-less outfits.
Roar host Sydney FC on Friday, while Wanderers are taking on Al Hilal in the AFC Champions League final first leg.
The winless Newcastle Jets face a tough trip to Wellington as Phoenix eye back-to-back wins on Sunday.
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