| 24. Round | 12/02/2022 | VfB Stuttgart II | - | 1. FSV Mainz 05 II | 0:2 |  |
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| 25. Round | 19/02/2022 | 1. FSV Mainz 05 II | - | FSV Frankfurt | 3:0 | ||||
| 26. Round | 26/02/2022 | FC 08 Homburg | - | 1. FSV Mainz 05 II | 3:2 | |
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| 27. Round | 04/03/2022 | 1. FSV Mainz 05 II | - | SV 07 Elversberg | 0:2 | ||||
| 28. Round | 12/03/2022 | Kickers Offenbach | - | 1. FSV Mainz 05 II | 2:0 | ||||
| 29. Round | 18/03/2022 | 1. FSV Mainz 05 II | - | SSV Ulm 1846 | 0:3 | |
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| 30. Round | 26/03/2022 | Rot-Weiß Koblenz | - | 1. FSV Mainz 05 II | 0:0 | |
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| 32. Round | 06/04/2022 | Hessen Kassel | - | 1. FSV Mainz 05 II | 2:1 | |
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| 33. Round | 10/04/2022 | 1. FSV Mainz 05 II | - | FC-Astoria Walldorf | 6:0 | |
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| 35. Round | 23/04/2022 | TSV Schott Mainz | - | 1. FSV Mainz 05 II | 0:0 | ||||
| 36. Round | 01/05/2022 | 1. FSV Mainz 05 II | - | FK Pirmasens | 4:1 |  |
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| 37. Round | 07/05/2022 | Bahlinger SC | - | 1. FSV Mainz 05 II | 0:2 | ||||
| 38. Round | 13/05/2022 | 1. FSV Mainz 05 II | - | TSG Balingen | 3:2 |
Germany