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Coach Gordon Igesund said on Thursday that Khumalo, who led the team at the recent Africa Cup of Nations (AFCON) tournament, lacked game time and was carrying a slight injury.
Itumeleng Khune would lead the side in Khumalo's absence.
“Everybody is aware that he played his first game for his team (Greek club PAOK) last week,” Igesund said after naming his 23-man squad.
“He's carrying a slight injury. I've chosen not to choose him on the strength that he has not been playing for his club.”
Igesund played down the significance of omitting the defender ahead of the crucial qualifying match.
“Sometimes we make too much of captaincy," he said.
"There are many players who are leaders and I think Khune will do a good job.”
Igesund made five changes to the squad that turned out at Afcon, with defenders Siboniso Gaxa and Khumalo making way for Russia-based Siyanda Xulu and Morgan Gould of Kaizer Chiefs.
Belgium-based Daylon Claasen makes a return to the squad, along with Dino Ndlovu, who plays his club football in Israel, and Daine Klate from Orlando Pirates.
Thulani Serero and Katlego Mphela were dropped, while Lehlohonolo Majoro was not considered due to injury.
“I did not make too many changes because I believe in continuity," Igesund said.
“We need to continue from where we left off in the AFCON tournament.
"I still believe we have a good chance of qualifying for Brazil in 2014, provided we win our upcoming match ang go and do well in the two away matches.
Igesund, taking charge of his first World Cup qualifier since he took the reins of the side in June last year, said CAR would be a difficult prospect.
Bafana are third in their qualifying group with two points - two adrift of leaders Ethiopia, and one behind second-placed CAR. Botswana are lying bottom of the table with one point.
“They are a very dangerous team. We will play them home and away and it is important for us to get the win at home," he said.
"They're very strong and physical, but if we can move the ball around and keep it on the ground we'll do well.”
Bafana Bafana squad:Goalkeepers: Itumeleng Khune, Senzo Meyiwa, Wayne Sandilands
Defenders: Morgan Gould, Siyabonga Sangweni, Thabo Nthethe, Anele Ngcongca, Siyanda Xulu, Tsepo Masilela, Thabo Matlaba
Midfielders: Kagisho Dikgacoi, Dean Furman, Reneilwe Letsholonyane, Oupa Mayisa, May Mahlangu, Daylon Claasen, Lerato Chabangu, Thuso Phala, Siphiwe Tshabalala, Daine Klate
Forwards: Bernard Parker, Dino Ndlovu, Tokelo Rantie
HAVE YOUR SAY: Bafana Bafana coach Gordon Igesund has named his 23-man squad for the SWC qualifier against Central African Republic. Katlego Mphela, Bongani Khumalo and Thulani Serero have been left out. What do you think? Send your thoughts to Sport24.
