Orlando Pirates, Supersport United and Wits University will be looking to make their mark on the rest of Africa as they kick off their various campaigns this weekend.
Pirates, the South African champions, will play Matlama, the Lesotho champions in Maseru on Sunday in a Confederation of African Football (CAF) champions league preliminary match.
Pirates, who last won the CAF club championship in 1995, do not know much of their opponents besides that they supply six players to the Lesotho national team.
The Buccaneers have left for Maseru without Andile Cele, Shaun Potgieter and Kabanga Tshamala who were not registered for the tournament because they were carrying injuries in December when the registration closed.
The marketing director of Pirates, Zodwa Khoza, says that they know very little about the Mountain Kingdom's soccer champions and they would not taking any chances by undermining them.
Supersport United will host Civics from Namibia on Saturday at the Loftus Stadium in the same competition.
Supersport only got to play in the Champions League because CAF wanted to make the tournament more attractive by inviting some of the countries to enter two teams.
Wits University is the third South Africa team that will be doing duties on the continent on Sunday when they play Maxaquene in Maputo in a Confederation Cup preliminary agme.
The return matches will be played in two weeks time.