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| H | Orense SC | - | Universidad Católica | 1:0 (0:0) | ||
| R | Universidad Católica | - | Orense SC | 3:1 (1:1) | ||
| H: 19.08.2022 20:30 | R: 26.08.2022 16:00 | Sieger: Universidad Católica | ||||
| H | Chacaritas FC | - | Deportivo Cuenca | 2:1 (2:0) | ||
| R | Deportivo Cuenca | - | Chacaritas FC | 3:1 (0:1) | ||
| H: 19.08.2022 22:00 | R: 28.08.2022 17:00 | Sieger: Deportivo Cuenca | ||||
| H | Manta FC | - | Emelec | 3:1 (1:0) | ||
| R | Emelec | - | Manta FC | 2:1 (0:0) | ||
| H: 19.08.2022 22:15 | R: 27.08.2022 20:00 | Sieger: Manta FC | ||||
| H | LDU Quito | - | Aucas | 3:2 (1:0) | ||
| R | Aucas | - | LDU Quito | 1:1 (0:0) | ||
| H: 20.08.2022 18:00 | R: 27.08.2022 17:00 | Sieger: LDU Quito | ||||
| H | Mushuc Runa | - | Independiente del Valle | 1:2 (1:1) | ||
| R | Independiente del Valle | - | Mushuc Runa | 3:1 (1:1) | ||
| H: 20.08.2022 18:45 | R: 27.08.2022 19:15 | Sieger: Independiente del Valle | ||||
| H | Barcelona | - | Olmedo | 0:3 (0:2) | ||
| R | Olmedo | - | Barcelona | 1:0 (1:0) | ||
| H: 20.08.2022 19:00 | R: 28.08.2022 21:15 | Sieger: Olmedo | ||||
| H | Atlético Santo Domingo | - | El Nacional | 3:0 (1:0) | ||
| R | El Nacional | - | Atlético Santo Domingo | 1:3 (1:1) | ||
| H: 21.08.2022 20:00 | R: 27.08.2022 21:00 | Sieger: Atlético Santo Domingo | ||||
| H | Macará | - | Guayaquil City | 3:1 (2:0) | ||
| R | Guayaquil City | - | Macará | 2:4 (1:0, 2:0, 2:0) i.E. | ||
| H: 25.08.2022 20:00 | R: 29.08.2022 18:00 | Sieger: Macará | ||||
