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| H | Al Merrikh SC | - | Al Ahly Tripolis | 2:0 (2:0) | ||
| R | Al Ahly Tripolis | - | Al Merrikh SC | 3:1 (2:1) | ||
| H: 07.10.2022 16:00 | R: 15.10.2022 19:00 | Sieger: Al Merrikh SC | ||||
| H | Young Africans | - | Al Hilal Omdurman | 1:1 (0:0) | ||
| R | Al Hilal Omdurman | - | Young Africans | 1:0 (1:0) | ||
| H: 08.10.2022 15:00 | R: 16.10.2022 20:00 | Sieger: Al Hilal Omdurman | ||||
| H | ASKO Kara | - | JS Kabylie | 1:2 (0:2) | ||
| R | JS Kabylie | - | ASKO Kara | 1:1 (1:0) | ||
| H: 08.10.2022 17:00 | R: 15.10.2022 20:00 | Sieger: JS Kabylie | ||||
| H | ASN Nigelec | - | Raja Casablanca | 0:2 (0:0) | ||
| R | Raja Casablanca | - | ASN Nigelec | 1:0 (0:0) | ||
| H: 08.10.2022 17:30 | R: 15.10.2022 19:00 | Sieger: Raja Casablanca | ||||
| H | Cape Town City FC | - | Petro Atlético | 0:3 (0:1) | ||
| R | Petro Atlético | - | Cape Town City FC | 1:0 (0:0) | ||
| H: 08.10.2022 18:00 | R: 14.10.2022 17:00 | Sieger: Petro Atlético | ||||
| H | Vipers SC | - | TP Mazembe | 0:0 (0:0) | ||
| R | TP Mazembe | - | Vipers SC | 2:4 (0:0, 0:0) i.E. | ||
| H: 09.10.2022 15:00 | R: 15.10.2022 15:00 | Sieger: Vipers SC | ||||
| H | Royal Leopards | - | Coton Sport Garoua | 1:1 (1:1) | ||
| R | Coton Sport Garoua | - | Royal Leopards | 2:1 (2:0) | ||
| H: 09.10.2022 15:00 | R: 16.10.2022 19:00 | Sieger: Coton Sport Garoua | ||||
| H | US Monastir | - | Al Ahly SC | 0:1 (0:0) | ||
| R | Al Ahly SC | - | US Monastir | 3:0 (2:0) | ||
| H: 09.10.2022 16:00 | R: 15.10.2022 18:00 | Sieger: Al Ahly SC | ||||
| H | La Passe FC | - | Mamelodi Sundowns | 0:7 (0:5) | ||
| R | Mamelodi Sundowns | - | La Passe FC | 8:1 (3:1) | ||
| H: 09.10.2022 16:00 | R: 14.10.2022 18:00 | Sieger: Mamelodi Sundowns | ||||
| H | Rivers United | - | Wydad AC | 2:1 (1:1) | ||
| R | Wydad AC | - | Rivers United | 6:0 (2:0) | ||
| H: 09.10.2022 17:00 | R: 16.10.2022 21:00 | Sieger: Wydad AC | ||||
| H | Plateau United | - | Espérance de Tunis | 2:1 (2:1) | ||
| R | Espérance de Tunis | - | Plateau United | 1:0 (0:0) | ||
| H: 09.10.2022 17:00 | R: 15.10.2022 18:00 | Sieger: Espérance de Tunis | ||||
| H | CD 1º de Agosto | - | Simba SC | 1:3 (0:1) | ||
| R | Simba SC | - | CD 1º de Agosto | 1:0 (1:0) | ||
| H: 09.10.2022 17:00 | R: 16.10.2022 15:00 | Sieger: Simba SC | ||||
| H | ASEC Mimosas | - | Horoya AC | 0:1 (0:0) | ||
| R | Horoya AC | - | ASEC Mimosas | 1:1 (0:0) | ||
| H: 09.10.2022 18:00 | R: 16.10.2022 18:00 | Sieger: Horoya AC | ||||
| H | Djoliba AC | - | CR Bélouizdad | 2:1 (1:1) | ||
| R | CR Bélouizdad | - | Djoliba AC | 2:0 (1:0) | ||
| H: 09.10.2022 18:00 | R: 14.10.2022 20:30 | Sieger: CR Bélouizdad | ||||
| H | Flambeau du Centre | - | Zamalek | 0:1 (0:1) | ||
| R | Zamalek | - | Flambeau du Centre | 5:1 (3:1) | ||
| H: 09.10.2022 19:00 | R: 14.10.2022 19:00 | Sieger: Zamalek | ||||
| H | RC Kadiogo | - | AS Vita Club | 0:0 (0:0) | ||
| R | AS Vita Club | - | RC Kadiogo | 4:3 (0:0, 0:0) i.E. | ||
| H: 16.10.2022 16:00 | R: 20.10.2022 16:30 | Sieger: AS Vita Club | ||||
