The Malian team reached the final of the 2012 competition only to lose 4-3 on aggregate to Congolese outfit Leopards.
But Djoliba's hopes of replicating that run appear slim following a 2-0 defeat at Wadi Degla in the first leg, a strike from midfielder Mostafa Talaat and a late Abdoulaye Traore own goal doing the damage for the Egyptain tournament debutants and leaving Karounga Keita's men on the brink of elimination.
SuperSport United are also in need of a turnaround in their home leg, but face a difficult task against 2006 winners and two-time finalists Etoile du Sahel.
Tunisian side Sahel lead 1-0 from the first leg thanks to a goal from defender Alaya Brigui, which put them in pole position to make another run towards the latter stages of the competition.
Sahel had the benefit of fortune in the first leg as South African club SuperSport saw a late equaliser from Mame Niang chalked off, much to the annoyance of coach Cavin Johnson.
But Johnson believes his side are still very much in the tie and is hopeful that SuperSport can go far in the tournament.
"We will come back and put up a big fight in the second leg," Johnson said.
"It will give me the greatest of pleasure if we get to the group stages. It would make the club proud. We can do well in this competition.
"South Africans need to take this tournament seriously and that's what we are doing right now."
Petro Luanda and Bizertin will have home advantage, but must be careful not to concede a possibly damaging away goal in their respective second-leg meetings with Ismaily and Warri Wolves after 0-0 first-leg draws.
An injury-time penalty from Menard Mupera gave Zimbabwean side How Mine a 2-1 first-leg success over Bayelsa United of Nigeria, whose away goal in that meeting could yet prove crucial.
Kigali and Constantine will both look to protect advantages and progress to the play-off round after 1-0 wins over Difaa El Jadida and ASEC Mimosas.
However, ZESCO United face a similar to predicament to Djoliba and will need to showcase a significant improvement versus Medeama, who cruised to a 2-0 triumph in the first leg as their impressive Confederation Cup bow rolls on.
