Khune is down with a chest infection while Keet is suffering from a knee injury.
Head coach Stuart Baxter has called up Reyaad Pieterse of SuperSport United as well as Wayne Sandilands of Orlando Pirates as replacements.
South Africa faces Cape Verde on Friday, 1 September at the Estadio Nacional Stadium in Cape Verde. Kick-off is at 17h30 local time (20h30 SA time).
The return leg will be played on Tuesday, 5 September at the Moses Mabhida Stadium in Durban. Kick-off is at 19h00.
Bafana Bafana will assemble for camp on Sunday in Johannesburg, and are expected to travel to Cape Verde on Tuesday.