| 2. Round | 13/02/2022 | Real Santa Cruz | - | CD Guabirá | 2:2 | ||||
| 3. Round | 18/02/2022 | Nacional Potosí | - | Real Santa Cruz | 1:0 | ||||
| 4. Round | 26/02/2022 | Real Santa Cruz | - | The Strongest | 1:2 |  |
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| 6. Round | 12/03/2022 | Real Santa Cruz | - | Always Ready | 0:1 | ||||
| 7. Round | 02/04/2022 | Real Santa Cruz | - | Oriente Petrolero | 2:1 | ||||
| 8. Round | 09/04/2022 | Atlético Palmaflor | - | Real Santa Cruz | 2:1 | |
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| 9. Round | 16/04/2022 | Universitario de Sucre | - | Real Santa Cruz | 2:3 | ||||
| 10. Round | 21/04/2022 | CD Guabirá | - | Real Santa Cruz | 1:0 | |
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| 11. Round | 24/04/2022 | Real Santa Cruz | - | Nacional Potosí | 3:2 | ||||
| 12. Round | 30/04/2022 | The Strongest | - | Real Santa Cruz | 1:1 | ||||
| 14. Round | 12/05/2022 | Club Aurora | - | Real Santa Cruz | 2:4 | ||||
| 15. Round | 14/05/2022 | Oriente Petrolero | - | Real Santa Cruz | 1:2 | |
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| 16. Round | 21/05/2022 | Real Santa Cruz | - | Atlético Palmaflor | 1:2 |
Dom. Republic