Reigning champions Setif, of Algeria, take on Gambian league champions Real de Banjul in what is the round of 32.
Setif sit second in the league, while Real have made an unbeaten start to their league campaign through nine matches.
The 2014 triumph was just Setif's second Champions League crown, having previously won it in 1988.
Raja Casablanca are three-time champions and they take on South Africa's Kaizer Chiefs.
Elsewhere, Zambia's ZESCO United take on Guinea's AS Kaloum, while USM Alger face Senegal's AS Pikine.
Malawi's Big Bullets do battle with Al Hilal, Coton Sport meet SM Sanga Balende and Esperance de Tunis face Cosmos de Bafia.
Sudan's Al Merrikh have a tie against Kabuscorp and AC Semassi take on Tunisians CS Sfaxien.
Asante Kotoko meet MC El Eulma, Enyimba face Smouha, AC Leopards will look to get past Gor Mahia and APR take on Al Ahly.
Moroccan league champions Moghreb Tetouan do battle with Kano Pillars, and Mamelodi Sundowns meet TP Mazembe.
AS Mangasport and Stade Malien also clash.
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