Three-time PSL champions SuperSport United, who were defeated in last year's Caf Confederation Cup final, will lock horns with Kenyan giants Gor Mahia in the play-off round.
Nicknamed K'Ogalo, Gor Mahia were demoted to the Confederation Cup, after they were knocked out of the Champions League by Tunisian giants Esperance Sportive de Tunis.
Established in 1968, K'Ogalo had qualified for the Champions League after winning the 2017 Kenyan Premier League title. Dylan Kerr's side dominated Kenyan football last year as they also clinched the Super Cup.
They are the most decorated club in the country having won the league title a record 16 times and they have also won the FKF President's Cup a record 10 times.
The Nairobi-based outfit remains the only club from Kenya to win an African continental title. In 1987, K'Ogalo reached the Caf African Cup Winners' Cup where they defeated Esperance and they clinched the trophy.
K'Ogalo had previously reached the final of the same competition in 1979 and they lost to Cameroonian side Canon Yaounde. The African Cup Winners' Cup was merged with the Caf Cup in 2004 to form the Caf Confederations Cup.
Gor Mahia's English coach Kerr will look to Meddie Kagere, Humphrey Mieno, Haron Shakava and Erick Bekoe as some of his key players against SuperSport.
Matsatsantsa eliminated K'Ogalo's biggest rivals in Kenya, AFC Leopards from the Confederation Cup in 2014. SuperSport's international experience should give them the edge over K'Ogalo.
The winner on aggregate between SuperSport and Gor Mahia will book their place in the group stage.
The reigning PSL champions Bidvest Wits were pitted against Nigerian giants Enyimba International FC in the Confederation Cup play-off round after being demoted from Champions League.
The Clever Boys were eliminated from the Champions League by Clube Desportivo 1º de Agosto and they will now take on one of Africa's top sides in Enyimba, who are considered to be the most successful club in Nigeria.
Affectionately known as the People's Elephant or Aba Warriors, Enyimba have won seven Nigeria Professional Football League (NPFL) titles and four Federation Cups since 2001.
They qualified for this year's Confederation Cup after finishing third in the 2017 NPFL standings - five points behind the champions Plateau United, who lost to Enyimba in their last two league meetings.
The Aba Warriors have a rich history in continental football. In 2003, they became the first Nigerian club to win the Africa's premier international club competition, Champions League and they successfully defended their title the following year.
Enyimba, who are under the guidance of Nigerian tactician Paul Aigbogun, have also won the Caf Super Cup twice and they are hoping to go all the way, and clinch the Confederation Cup for the first time since the club was established in 1976.
Ikechukwu Ezenwa, Mfon Udoh and Chinonso Okonkwo, who scored twice against Benin's Energie FC in the preliminary round, are the key players for People's Elephant.
The last time Enyimba faced a South African team in a continetal competition was in 2016. They beat Mamelodi Sundowns 1-0 at home in the Champions League Group B game, but they lost 2-1 in the return leg in Pretoria.
If Wits coach Gavin Hunt takes their play-off tie seriously and fields a strong team, the Clever Boys will stand a good chance of defeating Enyimba on aggregate and advance to the group stage for the first time.