| 2. Round | 12/02/2022 | Guaireña FC | - | Club Olimpia | 1:3 |  |
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| 3. Round | 20/02/2022 | Club Olimpia | - | Libertad | 2:2 | |
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| 6. Round | 13/03/2022 | Cerro Porteño | - | Club Olimpia | 0:2 | |
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| 7. Round | 20/03/2022 | Club Olimpia | - | Sportivo Ameliano | 0:2 | ||||
| 4. Round | 26/03/2022 | Sol de América | - | Club Olimpia | 0:1 | ||||
| 9. Round | 09/04/2022 | Club Olimpia | - | Club Nacional | 1:2 | ||||
| 10. Round | 16/04/2022 | 12 de Octubre de Itauguá | - | Club Olimpia | 0:0 | ||||
| 12. Round | 24/04/2022 | General Caballero DJLM | - | Club Olimpia | 2:3 |  |
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| 14. Round | 08/05/2022 | Libertad | - | Club Olimpia | 1:0 | ||||
| 15. Round | 11/05/2022 | Club Olimpia | - | Sol de América | 1:0 | ||||
| 16. Round | 16/05/2022 | Tacuary | - | Club Olimpia | 1:4 | |
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| 17. Round | 22/05/2022 | Club Olimpia | - | Cerro Porteño | 0:4 | ||||
| 18. Round | 14/06/2022 | Sportivo Ameliano | - | Club Olimpia | 1:4 | ||||
| 19. Round | 19/06/2022 | Club Olimpia | - | Resistencia SC | 6:1 | |
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| 20. Round | 23/06/2022 | Club Nacional | - | Club Olimpia | 1:1 | |
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| 21. Round | 26/06/2022 | Club Olimpia | - | 12 de Octubre de Itauguá | 4:1 | |
Uruguay