Holders Etoile du Sahel travel to Zimbabwe to play Dynamos on Sunday as they continue the defence of their African Champions League title.
The Tunisian side are among eight former winners of Africa's top club prize seeking to progress to the group phase of the tournament, which kicks off in July.
The losers from these ties will drop into in the Confederation Cup.
Etoile's French coach Bertrand Marchand, who has turned down the chance to take over as Tunisia coach, can choose from a full-strength squad for the first time in months.
However he will be reminded that Dynamos beat them 1-0 in Harare in the group phase of the competition a decade ago.
Clubs from north Africa are likely to dominate in the last knockout round, with a real chance that all eight qualifiers for the group phase will come from Arabic-speaking countries.
Last year's runners-up Al Ahly of Egypt play Platinum Stars from South Africa in Pretoria on Saturday.
It will be their first game in this year's tournament after two successive byes in previous rounds.
Coach Manuel Jose said he expected a tough game but that Al Ahly were intent on a winning start against their inexperienced opponents.
The Cairo giants clinched the Egyptian premier league for a fourth successive year on Monday and are likely to be in celebratory mood.
"We're going away from home and we're hoping to get a goal, or a draw would be good for us."
Zamalek, who went second in the Egyptian championship on Tuesday, have a home tie in Cairo on Saturday against Angola's InterClube.
Libya's Al Ittihad, semi-finalists last year along with Al Hilal of Sudan, have a home match against three times winners TP Mazembe of the DR Congo.
Al Hilal host South African champions Mamelodi Sundowns, whose domestic form has been on an upturn after a disappointing start to their league season.
"I'm hopeful, the team is gelling well and the confidence is back," Sundowns' Zimbabwe midfielder Esrom Nyandoro told BBC Sport.
"We're going away from home and we're hoping to get a goal, or a draw would be good for us.
"We don't know much about the team - but we know it's a strong side and we're hoping to keep the momentum going.
"To be honest the guys are tired, but we'll keep talking to each other, just to soldier on as players."
Tunisia's other representatives are Club Africain and they will be without striker Oussema Sellami for their match away to former champions Enyimba of Nigeria on Sunday.
The return legs will be played on the weekend of 9 to 11 May.
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