| 24 May 22 | r06     | Santos FCSantos FC | 1 - 1 | BanfieldBanfield |
| 24 May 22 | r06 | Unión La CaleraUnión La Cale | 3 - 2 | Universidad Católica del Universidad C |
| 25 May 22 | r06 | InternacionalInternacional | 5 - 1 | 9 de Octubre9 de Octubre |
| 25 May 22 | r06 | Independiente MedellínIndependiente | 1 - 1 | Guaireña FCGuaireña FC |
| 25 May 22 | r06 | LDU QuitoLDU Quito | 1 - 1 | Atletico GOAtletico GO |
| 25 May 22 | r06 | Defensa y JusticiaDefensa y Jus | 0 - 2 | Deportes AntofagastaDeportes Anto |
| 25 May 22 | r06 | LanusLanus | 1 - 0 | Metropolitanos F.C.Metropolitano |
| 25 May 22 | r06 | WanderersWanderers | 0 - 0 | Barcelona SCBarcelona SC |
| 25 May 22 | r06 | Sao PauloSao Paulo | 1 - 0 | Ayacucho FCAyacucho FC |
| 25 May 22 | r06 | WilstermannWilstermann | 0 - 2 | Everton de Viña del MarEverton de Vi |
| 26 May 22 | r06 | IndependienteIndependiente | 0 - 2 | CearaCeara |
| 26 May 22 | r06 | Real Esppor ClubReal Esppor C | 0 - 1 | General CaballeroGeneral Cabal |
| 26 May 22 | r06 | Racing ClubRacing Club | 0 - 1 | CA River PlateCA River Plat |
| 26 May 22 | r06 | FBC MelgarFBC Melgar | 3 - 1 | CuiabaCuiaba |
| 27 May 22 | r06 | Atlético JuniorAtlético Juni | 0 - 4 | UnionUnion |
| 27 May 22 | r06 | Oriente PetroleroOriente Petro | 1 - 10 | FluminenseFluminense |
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