| 17 May 22 | r05     | BanfieldBanfield | 1 - 1 | Universidad Católica del Universidad C |
| 17 May 22 | r05 | InternacionalInternacional | 2 - 0 | Independiente MedellínIndependiente |
| 17 May 22 | r05 | CearaCeara | 6 - 0 | General CaballeroGeneral Cabal |
| 18 May 22 | r05 | 9 de Octubre9 de Octubre | 2 - 3 | Guaireña FCGuaireña FC |
| 18 May 22 | r05 | Atletico GOAtletico GO | 1 - 0 | Deportes AntofagastaDeportes Anto |
| 18 May 22 | r05 | Atlético JuniorAtlético Juni | 2 - 0 | Oriente PetroleroOriente Petro |
| 18 May 22 | r05 | CA River PlateCA River Plat | 1 - 2 | CuiabaCuiaba |
| 18 May 22 | r05 | Ayacucho FCAyacucho FC | 0 - 2 | Everton de Viña del MarEverton de Vi |
| 19 May 22 | r05 | Racing ClubRacing Club | 1 - 0 | FBC MelgarFBC Melgar |
| 19 May 22 | r05 | Santos FCSantos FC | 1 - 0 | Unión La CaleraUnión La Cale |
| 19 May 22 | r05 | LDU QuitoLDU Quito | 2 - 2 | Defensa y JusticiaDefensa y Jus |
| 19 May 22 | r05 | IndependienteIndependiente | 4 - 0 | Real Esppor ClubReal Esppor C |
| 19 May 22 | r05 | UnionUnion | 0 - 0 | FluminenseFluminense |
| 20 May 22 | r05 | LanusLanus | 1 - 2 | WanderersWanderers |
| 20 May 22 | r05 | Metropolitanos F.C.Metropolitano | 2 - 2 | Barcelona SCBarcelona SC |
| 20 May 22 | r05 | Sao PauloSao Paulo | 3 - 0 | WilstermannWilstermann |
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