| 28 Feb 2021 12:00 | Spartak Moscow | 0 : 2 | Rubin Kazan | |
| 28 Feb 2021 17:00 | Krasnodar | : | Ural | |
| 28 Feb 2021 14:30 | Akhmat Grozny | 1 : 2 | Dinamo Moscow |
| 28 Feb 2021 15:00 | Angers SCO | 2 : 2 | Lens | |
| 28 Feb 2021 17:05 | Lille | 1 : 1 | Strasbourg | |
| 28 Feb 2021 15:00 | Lorient | 2 : 1 | Saint-Etienne | |
| 28 Feb 2021 13:00 | Monaco | 2 : 0 | Brest | |
| 28 Feb 2021 15:00 | Nîmes | 1 : 1 | Nantes | |
| 28 Feb 2021 15:00 | Reims | 0 : 0 | Montpellier | |
| 28 Feb 2021 21:00 | Olympique Marseille | 1 : 1 | Olympique Lyonnais |
| 28 Feb 2021 18:00 | Bayer 04 | 1 : 2 | Freiburg | |
| 28 Feb 2021 13:30 | Union Berlin | 1 : 1 | Hoffenheim | |
| 28 Feb 2021 15:30 | Mainz 05 | 0 : 1 | Augsburg |
| 28 Feb 2021 13:30 | 1. FC Heidenheim | : | Fortuna Düsseldorf | |
| 28 Feb 2021 13:30 | 1. FC Nürnberg | : | Eintracht Braunschweig | |
| 28 Feb 2021 13:30 | SV Sandhausen | : | VfL Osnabrück |
| 28 Feb 2021 17:30 | Chelsea | 0 : 0 | Manchester United | |
| 28 Feb 2021 13:00 | Crystal Palace | 0 : 0 | Fulham | |
| 28 Feb 2021 13:00 | Leicester City | 1 : 3 | Arsenal | |
| 28 Feb 2021 20:15 | Sheffield United | 0 : 2 | Liverpool | |
| 28 Feb 2021 15:00 | Tottenham Hotspur | 4 : 0 | Burnley |
| 28 Feb 2021 14:00 | Celta Vigo | 1 : 1 | Real Valladolid | |
| 28 Feb 2021 16:15 | Cádiz | : | Real Betis | |
| 28 Feb 2021 18:30 | Granada | : | Elche | |
| 28 Feb 2021 21:00 | Villarreal | : | Atletico Madrid |
| 28 Feb 2021 12:30 | Sampdoria | 0 : 2 | Atalanta | |
| 28 Feb 2021 18:00 | Napoli | 2 : 0 | Benevento | |
| 28 Feb 2021 15:00 | Crotone | 0 : 2 | Cagliari | |
| 28 Feb 2021 15:00 | Udinese | 1 : 0 | Fiorentina | |
| 28 Feb 2021 15:00 | Internazionale | 3 : 0 | Genoa | |
| 28 Feb 2021 20:45 | Roma | 1 : 2 | Milan |
| 2nd ht | CD Nacional | 1 : 2 | Sporting Braga | |
| 28 Feb 2021 20:00 | CD Santa Clara | : | Paços de Ferreira | |
| 28 Feb 2021 20:00 | FC Famalicão | : | SC Farense | |
| 28 Feb 2021 20:00 | FC Porto | : | Sporting CP | |
| 28 Feb 2021 20:00 | Moreirense | : | Belenenses SAD | |
| End | Portimonense | 0 : 0 | Marítimo | |
| 28 Feb 2021 20:00 | SL Benfica | : | Rio Ave | |
| End | Tondela | 1 : 0 | Gil Vicente FC | |
| 28 Feb 2021 20:00 | Vitória SC | : | Boavista |
| 28 Feb 2021 14:00 | ADO Den Haag | : | RKC Waalwijk | |
| 28 Feb 2021 14:00 | AZ Alkmaar | : | Feyenoord | |
| 28 Feb 2021 14:00 | FC Groningen | : | Fortuna Sittard | |
| 28 Feb 2021 14:00 | FC Utrecht | : | FC Emmen | |
| 28 Feb 2021 14:00 | Heracles Almelo | : | FC Twente | |
| 28 Feb 2021 14:00 | PEC Zwolle | : | Heerenveen | |
| 28 Feb 2021 14:00 | PSV Eindhoven | : | Ajax | |
| 28 Feb 2021 14:00 | Sparta Rotterdam | : | Willem II Tilburg | |
| 28 Feb 2021 14:00 | Vitesse | : | VVV-Venlo |
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