Kick off is at 15:00 (17:00GMT)
The start to the competition on Saturday ended goalless as Angola and Morocco drew 0-0 while hosts South Africa and Cape Verde produced a similar scoreline, all in Group A.
However, attention turns to Group B where the Black Stars, led by Asamoah Gyan meet the Leopards at the Nelson Mandela Bay Stadium in Port Elizabeth in the first match.
Ghana have had a good build up to the finals but Gyan is not getting ahead of himself.
“When we win our first game it's a very good start for the team,” said Ghana captain.
“I cannot predict that we will win [the Cup], but we must qualify from the group stages, and then we can start thinking about winning the cup.”
The Congolese have had an uneasy build-up after players refused to train on Thursday and Friday in order to force bonus payments for coaching staff that had not been paid for their participation in the tournament.
But with an experienced Nations Cup campaigner, coach Claude Le Roy in the seat, the Leopards are expected to turn up fighting.
Mali will take on Niger in the second game of the day.