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| 18.11.2021 | 21:15 | Sporting CP | - | Varzim SC | 2:1 (0:0) | |
| 19.11.2021 | 17:00 | Casa Pia AC | - | SC Farense | 3:1 (2:0) | |
| 19:45 | FC Penafiel | - | Portimonense SC | 0:3 (0:3) | ||
| 21:45 | SL Benfica | - | Paços de Ferreira | 4:1 (0:0) | ||
| 20.11.2021 | 12:00 | Leça FC | - | Gil Vicente | 1:0 (0:0) | |
| 15:00 | FC Vizela | - | Estrela Amadora | 2:0 (1:0) | ||
| 18:00 | Rio Ave FC | - | SC Olhanense | 2:1 (0:1) | ||
| 19:00 | Sporting Braga | - | CD Santa Clara | 6:0 (3:0) | ||
| 20:45 | FC Alverca | - | FC Famalicão | 1:2 (1:0) | ||
| 21:15 | FC Porto | - | CD Feirense | 5:1 (3:0) | ||
| 21.11.2021 | 12:00 | FC Serpa | - | GD Estoril | 0:5 (0:2) | |
| 15:00 | UD Vilafranquense | - | CD Mafra | 0:1 (0:0) | ||
| 15:00 | USC Paredes | - | União Torreense | 1:0 (1:0) | ||
| 15:00 | Caldas SC | - | Belenenses SAD | 3:5 (2:2) | ||
| 17:45 | Moreirense FC | - | Vitória Guimarães | 3:2 (2:0) | ||
| 22.11.2021 | 20:45 | CD Tondela | - | Leixões SC | 3:1 (1:0) |
