Blackburn defender Grant Hanley has pulled out of the Scotland squad to face Wales and Belgium with a groin injury.
And Norwich winger Robert Snodgrass is doubtful for the World Cup qualifying double header after being hit by an ankle problem.
Scotland assistant manager Peter Houston confirmed Hanley's withdrawal after the first training session at their Mar Hall base ahead of Friday's game in Cardiff.
Houston said: "Grant Hanley has a groin strain and he is going to miss out."
Houston added: "Snoddy was on the bench on Saturday with Norwich and never got on with his ankle, and it is still giving him a bit of trouble.
"We are just going to monitor that."
Scotland manager Craig Levein has not called up any replacement for Hanley and will make a decision over Snodgrass in the coming days.
Levein also has fitness decisions to make over midfielders Scott Brown and Darren Fletcher, who both missed the opening qualifying draws against Serbia and Macedonia.
Brown is managing an ongoing hip problem, which forced him out of Celtic's win over Hearts on Sunday, while Fletcher has made three appearances for Manchester United since returning to first-team action following a lay-off forced by a chronic bowel complaint.
However, Houston believes each player could conceivably play in both Cardiff and Brussels.
On Brown, Houston said: "He knows his body better than anybody.
"We'll have to monitor the situation but if he is confident he can handle both games, who are we to argue?
"He has made himself available, Celtic have made him available.
"If we don't think he is right for the second game then we will monitor that and take advice from the physios, doctors and Scott himself."
Fletcher, who did not feature for United in their victory at Newcastle on Sunday, did extra training on Monday along with Aston Villa right-back Alan Hutton and QPR forward Jamie Mackie, who were also left out of their club games.
And Houston was encouraged that the Scotland captain could play in both matches.
"He's certainly looking like that," the Dundee United manager said.
"It's fantastic to have him back. He is looking fit and strong. He is another one we have to monitor.
"He has certainly put himself up there for two games."
