The Ghana Football Association has confirmed the withdrawal of captain Asamoah Gyan and winger Thomas Agyepong from Saturday's 2018 Fifa World Cup qualifier against Uganda.
The duo have been forced out of coach James Kwesi Appiah's initial 26-man squad due to injury, leaving 24 men standing.
According to the football governing body, Columbus Crew duo Jonathan Mensah and Harrison Afful remain doubtful for the upcoming fixture after picking up injuries while in club action over the weekend.
The two men are expected to undergo further tests on Monday to "determine the extent of injuries".
Chasing his international debut, Malmo winger Kingsley Sarfo maintains his place in Appiah's squad following his release from police custody on Sunday, having been hit with a rape charge.
It is a make-or-break affair for the Black Stars as anything but three points against Uganda will end their chances of playing at a fourth successive World Cup.
Ahead of matchday five, the four-time African champions currently sit third in Group E, two and four points below the Cranes and Egypt respectively.
The Black Stars kicked off their campaign in a disappointing fashion, playing out a goalless draw at home to Uganda before falling 2-0 to Egypt on matchday two.
They finally got their first three points in a 5-1 away thrashing of Congo but only after they were held by the same side in the first leg four days earlier.
Appiah's men will play Egypt on the final matchday in November but unfavourable results in October's group matches will render the final hurdle a dead rubber.