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| H | ES Sétif | - | Espérance de Tunis | 0:0 (0:0) | ||
| R | Espérance de Tunis | - | ES Sétif | 0:1 (0:1) | ||
| H: 15.04.2022 23:00 | R: 22.04.2022 23:00 | Sieger: ES Sétif | ||||
| H | Petro Atlético | - | Mamelodi Sundowns | 2:1 (2:1) | ||
| R | Mamelodi Sundowns | - | Petro Atlético | 1:1 (0:0) | ||
| H: 16.04.2022 18:00 | R: 23.04.2022 18:00 | Sieger: Petro Atlético | ||||
| H | Al Ahly SC | - | Raja Casablanca | 2:1 (2:1) | ||
| R | Raja Casablanca | - | Al Ahly SC | 1:1 (1:1) | ||
| H: 16.04.2022 22:00 | R: 23.04.2022 00:00 | Sieger: Al Ahly SC | ||||
| H | CR Bélouizdad | - | Wydad AC | 0:1 (0:0) | ||
| R | Wydad AC | - | CR Bélouizdad | 0:0 (0:0) | ||
| H: 16.04.2022 23:00 | R: 24.04.2022 00:00 | Sieger: Wydad AC | ||||
