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| H | Forest Rangers | - | AS Bouenguidi | 0:0 (0:0) | ||
| R | AS Bouenguidi | - | Forest Rangers | 2:0 (0:0) | ||
| H: 28.11.2020 14:00 | R: 05.12.2020 15:30 | Sieger: AS Bouenguidi | ||||
| H | Vipers SC | - | Al Hilal Omdurman | 0:1 (0:1) | ||
| R | Al Hilal Omdurman | - | Vipers SC | 1:0 (0:0) | ||
| H: 28.11.2020 14:00 | R: 06.12.2020 14:00 | Sieger: Al Hilal Omdurman | ||||
| H | APR FC | - | Gor Mahia FC | 2:1 (1:1) | ||
| R | Gor Mahia FC | - | APR FC | 3:1 (1:0) | ||
| H: 28.11.2020 14:00 | R: 05.12.2020 14:00 | Sieger: Gor Mahia FC | ||||
| H | Jwaneng Galaxy | - | US Zilimadjou | 4:0 (2:0) | ||
| R | US Zilimadjou | - | Jwaneng Galaxy | 1:1 (0:0) | ||
| H: 28.11.2020 14:30 | R: 06.12.2020 13:00 | Sieger: Jwaneng Galaxy | ||||
| H | Mlandege | - | CS Sfaxien | 0:5 (0:2) | ||
| R | CS Sfaxien | - | Mlandege | 3:1 (0:0) | ||
| H: 28.11.2020 14:30 | R: 05.12.2020 15:00 | Sieger: CS Sfaxien | ||||
| H | CD Costa do Sol | - | FC Platinum | 1:2 (0:0) | ||
| R | FC Platinum | - | CD Costa do Sol | 2:0 (0:0) | ||
| H: 28.11.2020 14:30 | R: 05.12.2020 14:00 | Sieger: FC Platinum | ||||
| H | Buffles du Borgou FC | - | MC Alger | 1:1 (0:1) | ||
| R | MC Alger | - | Buffles du Borgou FC | 5:1 (2:1) | ||
| H: 28.11.2020 15:00 | R: 19.12.2020 20:45 | Sieger: MC Alger | ||||
| H | Al Ahly Benghazi | - | Mekelle 70 Enderta | 3:0 Wert. | ||
| R | Mekelle 70 Enderta | - | Al Ahly Benghazi | 0:3 Wert. | ||
| H: 28.11.2020 19:00 | R: 05.12.2020 14:00 | Sieger: Al Ahly Benghazi | ||||
| H | Young Buffaloes | - | Le Messager Ngozi | 0:0 (0:0) | ||
| R | Le Messager Ngozi | - | Young Buffaloes | 1:1 (1:1) | ||
| H: 29.11.2020 14:00 | R: 06.12.2020 14:00 | Sieger: Young Buffaloes | ||||
| H | PWD Bamenda | - | Kaizer Chiefs | 0:1 (0:0) | ||
| R | Kaizer Chiefs | - | PWD Bamenda | 0:0 (0:0) | ||
| H: 29.11.2020 15:00 | R: 05.12.2020 18:00 | Sieger: Kaizer Chiefs | ||||
| H | Bantu Mafeteng | - | Nkana FC | 0:1 (0:1) | ||
| R | Nkana FC | - | Bantu Mafeteng | 0:0 (0:0) | ||
| H: 29.11.2020 15:00 | R: 05.12.2020 14:00 | Sieger: Nkana FC | ||||
| H | AS Otôho | - | Al Merrikh SC | 1:1 (0:0) | ||
| R | Al Merrikh SC | - | AS Otôho | 2:0 (0:0) | ||
| H: 29.11.2020 15:30 | R: 04.12.2020 14:00 | Sieger: Al Merrikh SC | ||||
| H | FC Akonangui | - | Petro Atlético | 0:1 (0:1) | ||
| R | Petro Atlético | - | FC Akonangui | 2:2 (1:0) | ||
| H: 29.11.2020 15:30 | R: 05.12.2020 17:00 | Sieger: Petro Atlético | ||||
| H | AS SONIDEP | - | Mogadishu City Club | 2:0 (0:0) | ||
| R | Mogadishu City Club | - | AS SONIDEP | 0:2 (0:2) | ||
| H: 29.11.2020 16:00 | R: 05.12.2020 15:15 | Sieger: AS SONIDEP | ||||
| H | Gazelle FC | - | CF Garde Républicaine | 3:0 Wert. | ||
| R | CF Garde Républicaine | - | Gazelle FC | 0:3 Wert. | ||
| H: 29.11.2020 16:00 | R: 04.12.2020 15:00 | Sieger: Gazelle FC | ||||
| H | Plateau United | - | Simba SC | 0:1 (0:0) | ||
| R | Simba SC | - | Plateau United | 0:0 (0:0) | ||
| H: 29.11.2020 16:00 | R: 05.12.2020 15:15 | Sieger: Simba SC | ||||
| H | RC Abidjan | - | ASKO Kara | 1:0 (1:0) | ||
| R | ASKO Kara | - | RC Abidjan | 2:1 (0:1) | ||
| H: 29.11.2020 17:00 | R: 06.12.2020 16:30 | Sieger: RC Abidjan | ||||
| H | Rahimo FC | - | Enyimba Aba | 0:1 (0:0) | ||
| R | Enyimba Aba | - | Rahimo FC | 1:1 (0:0) | ||
| H: 29.11.2020 17:00 | R: 06.12.2020 16:00 | Sieger: Enyimba Aba | ||||
| H | FC Nouadhibou | - | Asante Kotoko | 1:1 (1:1) | ||
| R | Asante Kotoko | - | FC Nouadhibou | 2:0 Wert. | ||
| H: 29.11.2020 17:00 | R: 06.12.2020 17:00 | Sieger: Asante Kotoko | ||||
| H | CR Bélouizdad | - | Al Nasr Benghazi | 2:0 (1:0) | ||
| R | Al Nasr Benghazi | - | CR Bélouizdad | 0:2 (0:1) | ||
| H: 29.11.2020 17:00 | R: 06.12.2020 17:00 | Sieger: CR Bélouizdad | ||||
| H | AS Ashanti Golden Boys | - | Stade Malien | 1:2 (0:2) | ||
| R | Stade Malien | - | AS Ashanti Golden Boys | 2:0 Wert. | ||
| H: 29.11.2020 17:30 | R: 05.12.2020 17:15 | Sieger: Stade Malien | ||||
| H | Armed Forces FC | - | Teungueth FC | 1:1 (1:0) | ||
| R | Teungueth FC | - | Armed Forces FC | 2:0 (0:0) | ||
| H: 29.11.2020 17:30 | R: 06.12.2020 18:00 | Sieger: Teungueth FC | ||||
