| 05 Apr 22 | r01     | Universidad Católica del Universidad C | 0 - 0 | Unión La CaleraUnión La Cale |
| 05 Apr 22 | r01 | BanfieldBanfield | 1 - 0 | Santos FCSantos FC |
| 05 Apr 22 | r01 | CearaCeara | 2 - 1 | IndependienteIndependiente |
| 06 Apr 22 | r01 | Everton de Viña del MarEverton de Vi | 1 - 1 | WilstermannWilstermann |
| 06 Apr 22 | r01 | Atletico GOAtletico GO | 4 - 0 | LDU QuitoLDU Quito |
| 06 Apr 22 | r01 | General CaballeroGeneral Cabal | 1 - 1 | Real Esppor ClubReal Esppor C |
| 06 Apr 22 | r01 | FluminenseFluminense | 3 - 0 | Oriente PetroleroOriente Petro |
| 06 Apr 22 | r01 | UnionUnion | 1 - 1 | Atlético JuniorAtlético Juni |
| 07 Apr 22 | r01 | 9 de Octubre9 de Octubre | 2 - 2 | InternacionalInternacional |
| 07 Apr 22 | r01 | Deportes AntofagastaDeportes Anto | 1 - 3 | Defensa y JusticiaDefensa y Jus |
| 07 Apr 22 | r01 | CuiabaCuiaba | 2 - 0 | FBC MelgarFBC Melgar |
| 07 Apr 22 | r01 | CA River PlateCA River Plat | 0 - 1 | Racing ClubRacing Club |
| 08 Apr 22 | r01 | Barcelona SCBarcelona SC | 4 - 2 | WanderersWanderers |
| 08 Apr 22 | r01 | Metropolitanos F.C.Metropolitano | 0 - 0 | LanusLanus |
| 08 Apr 22 | r01  | Ayacucho FCAyacucho FC | 2 - 3 | Sao PauloSao Paulo |
| 08 Apr 22 | r01 | Guaireña FCGuaireña FC | 3 - 3 | Independiente MedellínIndependiente |
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