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| 15/10/2021 | 19:45 | Flint Town United | - | Connah's Quay Nomads | 0:2 | |
| 16/10/2021 | 12:45 | Colwyn Bay FC | - | Cardiff Metropolitan | 1:0 | |
| 14:00 | Saltney Town | - | Aberystwyth Town | 4:5 pso | ||
| 14:30 | Haverfordwest County | - | Bala Town | 1:3 | ||
| 14:30 | Carmarthen Town | - | The New Saints | 4:5 pso | ||
| 14:30 | Penybont FC | - | Caernarfon Town | 3:1 pso | ||
| 14:30 | Buckley Town | - | Taff's Well AFC | 0:2 | ||
| 14:30 | Swansea University | - | Guilsfield FC | 1:2 |
