Scott McTominay has left the Scotland camp after contracting a "throat virus", Steve Clarke confirmed.
The Manchester United midfielder will miss Friday's World Cup qualifier at Moldova because of the illness.
Scotland have been training in Spain this week ahead of the trip but McTominay was sent home.
Clarke retains hope, however, that McTominay will be able to overcome the virus over the weekend and be available for selection on Monday when Scotland face Denmark – who have already booked their spot for the World Cup – in their last match in their qualifying group stage.
"Unfortunately, Scott McTominay has picked up a bit of a throat virus, so we have sent Scott home to rest and recuperate and hopefully join us again at the weekend," Clarke told reporters.
Scotland, who are four points ahead of third-placed Israel, need just one win from their final two matches to make sure of second spot in Group F, subsequently confirming their participation in the play-offs next March.
Clarke should be confident of getting the job done without McTominay on Friday given hosts Moldova have taken just one point from their eight matches.
But how the virus develops could impact McTominay's employers, Man Utd.
Should it take McTominay longer than initially expected to get over the illness, he could potentially be a doubt for United's trip to Watford on November 20, which could be problematic given boss Ole Gunnar Solskjaer is likely going to be without the injured Paul Pogba.
France star Pogba suffered a thigh injury during training for Les Bleus and was sent back to United. While no timeframe has been put on his recovery, reports suggest he could be out until January.