Scotland will be without Newcastle winger Ryan Fraser and Norwich defender Grant Hanley for Thursday's must-win Euro 2020 play-off against Serbia.
Fraser had started Scotland's last two games but he missed Newcastle's defeat at Southampton on Friday due to a hamstring injury, while Hanley is struggling with a similar problem.
Scotland assistant coach Steven Reid on Monday revealed the pair will not be fit for the crucial clash in Belgrade, which offers the winners a place at the delayed Euro 2020.
The Scots have not appeared in a major tournament since the 1998 World Cup.
"Ryan and Grant Hanley at the moment are struggling. It's disappointing. Grant has missed a little bit of football and unfortunately is not going to be with us, and Ryan as well," Reid said.
"He performed really well in the past camp so that is a blow but we have got strength in depth.
"We have obviously bigger numbers than usual in the squad and feel as if we have a squad which is capable of competing well at our strongest in the Serbia game and going into the two Nations League games after."
Scotland were hit by fitness issues during the last international break as well when a positive Covid-19 test for Stuart Armstrong also took Ryan Christie and Kieran Tierney out of the squad.
Steve Clarke's team still managed to beat Israel in the play-off semi-final and defeat Slovakia and Czech Republic in the Nations League.
Reid believes the experience of thriving with an under-manned squad will serve Scotland well when they face Serbia before finishing their Nations League campaign against Slovakia and Israel.
"What has been pleasing in the last couple of camps is, despite the injuries and the issues with the Covid situation, the lads that stepped up were first class and that's going to be the same going into all of these games as well," Reid said.
"If there was to be an issue, we have players who have stepped in and stepped up to the plate."