| 5. Round | 24/04/2021 | Club San José | - | CD Guabirá | 0:1 |  |
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| 6. Round | 04/05/2021 | Blooming | - | Club San José | 4:0 | |
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| 7. Round | 08/05/2021 | Club San José | - | Bolívar | 0:5 | |
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| 11. Round | 26/07/2021 | Real Santa Cruz | - | Club San José | 5:0 | ||||
| 13. Round | 04/08/2021 | Oriente Petrolero | - | Club San José | 4:0 | ||||
| 14. Round | 07/08/2021 | Club San José | - | The Strongest | 0:1 | |
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| 15. Round | 15/08/2021 | Jorge Wilstermann | - | Club San José | 4:0 | ||||
| 16. Round | 18/08/2021 | Atlético Palmaflor | - | Club San José | 1:0 | ||||
| 17. Round | 21/08/2021 | Club San José | - | Always Ready | 0:4 | ||||
| 18. Round | 11/09/2021 | Royal Pari | - | Club San José | 6:1 | ||||
| 19. Round | 17/09/2021 | Club San José | - | Real Potosí | 0:0 | |
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| 21. Round | 25/09/2021 | Club San José | - | Blooming | 1:2 | |
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| 24. Round | 27/10/2021 | Real Tomayapo | - | Club San José | 1:0 | ||||
| 25. Round | 01/11/2021 | Independiente Petrolero | - | Club San José | 4:0 | ||||
| 26. Round | 22/11/2021 | Club San José | - | Real Santa Cruz | 1:2 | ||||
| 27. Round | 26/11/2021 | Nacional Potosí | - | Club San José | 7:1 | ||||
| 28. Round | 30/11/2021 | Club San José | - | Oriente Petrolero | 0:2 |
Bolivia