Wales midfielder Joe Allen and striker Ched Evans have been ruled out of Friday's Euro 2012 qualifier against Bulgaria.
Both players have been struggling with groin injuries this week and have returned to their clubs, Swansea and Sheffield United respectively, for treatment.
Caretaker manager Brian Flynn will determine after the Bulgaria game whether either can rejoin the squad for next week's trip to Switzerland.
Flynn said: "Both have gone back to their clubs for intensive treatment and we are going to reassess the situation on Saturday."
The loss of Evans further depletes Flynn's attacking options having lost Craig Bellamy and Rob Earnshaw to injury.
Earnshaw pulled out on Monday with a thigh injury and was replaced by untried Southampton forward Ryan Doble, 19.
Bellamy, the team's captain and talisman, was not named in the squad last Friday because of a knee injury but then surprisingly played - and scored - for Cardiff the following day.
Flynn, who has been placed in temporary charge for the Bulgaria and Switzerland fixtures, has again insisted he has no issue with Cardiff manager Dave Jones over that matter.
The former Wrexham and Swansea boss said: "We go back a long way in terms of being enemies in the dugout and friends afterwards. It is a good relationship. He has bought players off me and I have got more money out of him when he has bought my players. We get on.
"I don't think Craig could play. I saw him on Tuesday and David informed me then he was still a little sore, so it is unlikely he would have been fit anyway - so I am led to believe."