| 1. Round | 18/07/2021 | Club Olimpia | - | River Plate | 1:3 | ||||
| 2. Round | 27/07/2021 | 12 de Octubre de Itauguá | - | Club Olimpia | 1:3 |  |
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| 3. Round | 02/08/2021 | Club Olimpia | - | Guaireña FC | 0:2 | ||||
| 7. Round | 28/08/2021 | Club Olimpia | - | Sol de América | 0:1 | ||||
| 8. Round | 13/09/2021 | Libertad | - | Club Olimpia | 0:3 | ||||
| 9. Round | 21/09/2021 | Club Olimpia | - | Club Nacional | 1:2 | ||||
| 10. Round | 26/09/2021 | River Plate | - | Club Olimpia | 1:2 | |
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| 11. Round | 02/10/2021 | Club Olimpia | - | 12 de Octubre de Itauguá | 1:2 | ||||
| 12. Round | 18/10/2021 | Guaireña FC | - | Club Olimpia | 0:2 | |
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| 13. Round | 24/10/2021 | Club Olimpia | - | Guaraní | 1:3 | ||||
| 14. Round | 31/10/2021 | Cerro Porteño | - | Club Olimpia | 1:0 | ||||
| 17. Round | 26/11/2021 | Club Olimpia | - | Libertad | 2:3 | |
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| 18. Round | 05/12/2021 | Club Nacional | - | Club Olimpia | 1:3 | |
Uruguay