| 2. Round | 05/09/2021 | Unionistas CF | - | Cultural Leonesa | 2:2 |  |
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| 3. Round | 12/09/2021 | Cultural Leonesa | - | Athletic Club B | 2:1 | ||||
| 5. Round | 25/09/2021 | Cultural Leonesa | - | Real Valladolid B | 4:2 | ||||
| 10. Round | 30/10/2021 | CD Tudelano | - | Cultural Leonesa | 1:1 | ||||
| 11. Round | 07/11/2021 | Cultural Leonesa | - | Racing Santander | 3:0 | ||||
| 12. Round | 12/11/2021 | SD Logroñés | - | Cultural Leonesa | 1:1 |  |
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| 13. Round | 20/11/2021 | Cultural Leonesa | - | UD SS Reyes | 2:0 | |
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| 14. Round | 28/11/2021 | CD Calahorra | - | Cultural Leonesa | 2:0 | ||||
| 15. Round | 05/12/2021 | Cultural Leonesa | - | RC Celta B | 0:1 | ||||
| 16. Round | 11/12/2021 | Zamora CF | - | Cultural Leonesa | 2:2 | ||||
| 19. Round | 22/01/2022 | Cultural Leonesa | - | Real Unión | 1:1 | |
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| 20. Round | 25/01/2022 | Athletic Club B | - | Cultural Leonesa | 1:2 | |
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| 21. Round | 29/01/2022 | Cultural Leonesa | - | CD Badajoz | 1:0 | |
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| 22. Round | 09/03/2022 | Racing Santander | - | Cultural Leonesa | 4:0 | |
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| 35. Round | 08/05/2022 | RC Celta B | - | Cultural Leonesa | 5:3 | |
Spain