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| H | Niki Volou FC | - | Panetolikos | 0:1 (0:1) | ||
| R | Panetolikos | - | Niki Volou FC | 1:0 (0:0) | ||
| H: 01.12.2021 14:00 | R: 22.12.2021 16:00 | Sieger: Panetolikos | ||||
| H | Aris Saloniki | - | OFI Heraklion | 3:1 (2:0) | ||
| R | OFI Heraklion | - | Aris Saloniki | 0:2 (0:0) | ||
| H: 01.12.2021 16:00 | R: 23.12.2021 14:00 | Sieger: Aris Saloniki | ||||
| H | Levadiakos | - | Olympiakos Piraeus | 3:2 (2:1) | ||
| R | Olympiakos Piraeus | - | Levadiakos | 2:0 (2:0) | ||
| H: 01.12.2021 16:00 | R: 22.12.2021 18:00 | Sieger: Olympiakos Piraeus | ||||
| H | Panathinaikos | - | Volos NFC | 2:1 (1:0) | ||
| R | Volos NFC | - | Panathinaikos | 0:0 (0:0) | ||
| H: 01.12.2021 18:00 | R: 23.12.2021 16:00 | Sieger: Panathinaikos | ||||
| H | AEK Athen | - | AE Kifisias | 4:0 (0:0) | ||
| R | AE Kifisias | - | AEK Athen | 1:1 (0:0) | ||
| H: 01.12.2021 19:15 | R: 23.12.2021 18:00 | Sieger: AEK Athen | ||||
| H | AE Lárissa | - | PAOK Saloniki | 1:1 (0:0) | ||
| R | PAOK Saloniki | - | AE Lárissa | 3:1 (1:0) | ||
| H: 01.12.2021 20:30 | R: 22.12.2021 16:00 | Sieger: PAOK Saloniki | ||||
| H | Agios Nikolaos | - | Anagennisi Karditsa | 0:1 (0:0) | ||
| R | Anagennisi Karditsa | - | Agios Nikolaos | 5:0 (1:0) | ||
| H: 02.12.2021 14:00 | R: 22.12.2021 14:00 | Sieger: Anagennisi Karditsa | ||||
| H | Lamia | - | Ionikos Nikea | 2:0 (1:0) | ||
| R | Ionikos Nikea | - | Lamia | 0:1 (0:1) | ||
| H: 02.12.2021 16:00 | R: 23.12.2021 16:00 | Sieger: Lamia | ||||
