| 1. Round | 25/07/2021 | MŠK Žilina | - | ŠKF Sereď | 3:0 | ||||
| 2. Round | 30/07/2021 | ŠKF Sereď | - | MFK Ružomberok | 2:3 |  |
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| 3. Round | 08/08/2021 | ŠKF Sereď | - | FC DAC 1904 | 1:0 | ||||
| 4. Round | 14/08/2021 | FK Pohronie | - | ŠKF Sereď | 1:1 | ||||
| 5. Round | 22/08/2021 | ŠKF Sereď | - | Slovan Bratislava | 0:1 | ||||
| 6. Round | 28/08/2021 | AS Trenčín | - | ŠKF Sereď | 0:0 | ||||
| 9. Round | 25/09/2021 | ŠKF Sereď | - | MFK Zemplín Michalovce | 0:1 | ||||
| 10. Round | 02/10/2021 | ŠKF Sereď | - | FK Senica | 2:1 | ||||
| 11. Round | 16/10/2021 | Zlaté Moravce | - | ŠKF Sereď | 2:2 | ||||
| 12. Round | 22/10/2021 | ŠKF Sereď | - | MŠK Žilina | 1:1 | ||||
| 13. Round | 30/10/2021 | MFK Ružomberok | - | ŠKF Sereď | 3:1 | |
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| 14. Round | 06/11/2021 | FC DAC 1904 | - | ŠKF Sereď | 1:3 | ||||
| 15. Round | 20/11/2021 | ŠKF Sereď | - | FK Pohronie | 3:1 | ||||
| 16. Round | 29/11/2021 | Slovan Bratislava | - | ŠKF Sereď | 2:0 | ||||
| 17. Round | 04/12/2021 | ŠKF Sereď | - | AS Trenčín | 4:2 | |
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| 18. Round | 11/12/2021 | Tatran Liptovský Mikuláš | - | ŠKF Sereď | 1:1 | ||||
| 19. Round | 18/12/2021 | ŠKF Sereď | - | Spartak Trnava | 0:1 | ||||
| 20. Round | 11/02/2022 | MFK Zemplín Michalovce | - | ŠKF Sereď | 0:1 | ||||
| 22. Round | 26/02/2022 | ŠKF Sereď | - | Zlaté Moravce | 2:1 | |
Germany