| 11. Round | 16/10/2021 | FK Senica | - | MFK Zemplín Michalovce | 1:1 | ||||
| 13. Round | 30/10/2021 | MFK Zemplín Michalovce | - | FK Pohronie | 0:2 |  |
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| 14. Round | 05/11/2021 | AS Trenčín | - | MFK Zemplín Michalovce | 4:2 |  |
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| 15. Round | 21/11/2021 | MFK Zemplín Michalovce | - | Slovan Bratislava | 1:2 | ||||
| 18. Round | 10/12/2021 | Spartak Trnava | - | MFK Zemplín Michalovce | 2:0 | ||||
| 20. Round | 11/02/2022 | MFK Zemplín Michalovce | - | ŠKF Sereď | 0:1 | ||||
| 21. Round | 19/02/2022 | MŠK Žilina | - | MFK Zemplín Michalovce | 2:1 | ||||
| 22. Round | 26/02/2022 | MFK Zemplín Michalovce | - | FK Senica | 0:1 |
Spain