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| 21/09/2021 | 13:00 | Şomuz Fălticeni | - | FC Voluntari | 1:4 (1:1) | |
| 14:00 | Minaur Baia Mare | - | FC Politehnica Iași | 3:1 (1:1) | ||
| 16:45 | Petrolul Ploieşti | - | FC Universitatea Craiova | 0:1 (0:0) | ||
| 19:30 | CS Mioveni | - | Rapid Bucureşti | 4:5 (0:0, 0:0, 0:0) pso | ||
| 22/09/2021 | 13:00 | Argeș Pitești | - | FC Botoşani | 4:2 (0:0, 0:0, 0:0) pso | |
| 14:30 | CSM Slatina | - | FC Dunărea Călărași | 1:2 (1:0) | ||
| 14:30 | FK Csikszereda | - | Chindia Târgoviște | 0:1 (0:1) | ||
| 14:30 | Unirea Slobozia | - | SSU Poli Timişoara | 0:1 (0:0) | ||
| 14:30 | Concordia Chiajna | - | Gaz Metan Mediaş | 0:1 (0:0, 0:0) aet | ||
| 14:30 | FC Buzău | - | Academica Clinceni | 2:1 (0:1, 1:1) aet | ||
| 14:30 | ASC Oradea | - | FC Hermannstadt | 0:1 (0:0) | ||
| 16:00 | Farul Constanța | - | Sepsi OSK | 0:1 (0:0) | ||
| 19:00 | FC Hunedoara | - | FCSB | 3:5 (0:2, 3:3) aet | ||
| 23/09/2021 | 14:00 | CSO Filiaşi | - | UTA Arad | 1:0 (1:0) | |
| 16:45 | Ripensia Timisoara | - | Dinamo Bucureşti | 0:1 (0:1) | ||
| 19:30 | CS Universitatea Craiova | - | CFR Cluj | 1:0 (0:0) |
