Neighbours Mali and Guinea meet each other in a competitive fixture for the first time in eight years as they kick off their 2012 campaign.
Mali have been hit by a succession of injuries in the build-up, with striker Mahamane Traore the latest to be affected - this time, with a foot problem.
The Eagles had already lost Mohamed Fofana and Khalilou Traore, calling up Ousmane Berthe and Souleymane Keita in their place.
Guinea mix youth and experience, with the likes of Bobo Balde joining hopefuls like Abdoul Razzagui Camara.
In a competitive Group D line-up, many see Mali and Guinea as the main contenders to fight it out for two places with Ghana - providing Botswana do not upset the odds.
In the absence of Momo Sissoko and Frederic Kanoute, Barcelona's Seydou Keita and Mali captain Cedric Kante must help youngsters such as Samba Diakite and Samba Sow settle on the big stage.
"It will be a very difficult game but we have often enjoyed the luck against Guinea at this tournament," said midfielder Keita.
"But this is a very different tournament in many ways. First, Mali are here with a very young team and also this will be our opening match in this competition."
Mali are gambling on the fitness of Mahamane Traore after initially choosing to replace him in the squad with Cheick Fantamady Diarra, a change which the Confederation of African Football processed, only to have a change of heart later on.
However, the Metz midfielder, 23, will be out for 10 days at least, according to Mali's team doctors.
Despite Mali's long-standing pedigree in the competition, Guinea have enjoyed more recent success, reaching the quarter-finals in 2006 and 2008.
French coach Michel Dussuyer has emphasised the difficult task facing his side in Group D, however.
"Our first objective is to get past the first round," he said. "Ghana and Mali will be our major rivals, but we will not take Botswana, who were the surprise team in the qualifiers, for granted."