Last year, the Tunisian outfit reached the semi-finals of the competition, before being knocked out 1-0 on aggregate by eventual winners and fellow countrymen Sfaxien.
This time around they begin their campaign with a tie against Angolan opposition Huila, who lost the opening game of their domestic season on Saturday.
Djoliba, runners-up in 2012, travel to Democratic Republic of Congo to take on Don Bosco, while Supersport United of South Africa host Kenya's AFC Leopards.
Winners of the tournament in 2006 and unbeaten in 11 Tunisian Ligue 1 matches, Etoile Sahel will be confident when they travel to Congo's CARA Brazzaville, whose countrymen Kondzo will host Nigerian outfit Bayelsa United.
Egyptian Premier League contenders Ismaily visit MK Etancheite while Algerians CS Constantine host Red Lions, who are struggling in the Liberian top flight.
Malian outfit COB host ASEC Mimosas, who sit second in Ivory Coast's Ligue 1, and Ebusua Dwarfs will be hoping to establish a first-leg lead when they take on Petro de Luanda.
Elsewhere, ZESCO United visit Ferroviario Beira, Douanes Lome welcome Wadi Degla and Difaa El Jadida travel to Gambia to take on Gamtel.
