| 2. Round | 13/03/2021 | Atlético Palmaflor | - | Real Santa Cruz | 1:0 | ||||
| 1. Round | 28/03/2021 | Real Santa Cruz | - | Jorge Wilstermann | 0:2 | ||||
| 3. Round | 03/04/2021 | Real Santa Cruz | - | Always Ready | 2:3 | ||||
| 4. Round | 09/04/2021 | Royal Pari | - | Real Santa Cruz | 3:2 | ||||
| 6. Round | 02/05/2021 | CD Guabirá | - | Real Santa Cruz | 1:0 | ||||
| 7. Round | 07/05/2021 | Real Santa Cruz | - | Blooming | 1:0 |  |
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| 5. Round | 12/05/2021 | Real Santa Cruz | - | Real Potosí | 4:1 | |
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| 8. Round | 12/07/2021 | Bolívar | - | Real Santa Cruz | 1:1 | |
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| 9. Round | 17/07/2021 | Real Santa Cruz | - | Club Aurora | 1:1 | ||||
| 10. Round | 21/07/2021 | Real Tomayapo | - | Real Santa Cruz | 2:1 | ||||
| 14. Round | 07/08/2021 | Real Santa Cruz | - | Oriente Petrolero | 0:0 | ||||
| 15. Round | 15/08/2021 | The Strongest | - | Real Santa Cruz | 1:2 | |
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| 16. Round | 20/08/2021 | Jorge Wilstermann | - | Real Santa Cruz | 5:1 | |
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| 18. Round | 14/09/2021 | Always Ready | - | Real Santa Cruz | 4:0 |
Bolivia