| 26 Apr 22 | r03     | Real Esppor ClubReal Esppor C | 0 - 2 | IndependienteIndependiente |
| 26 Apr 22 | r03 | General CaballeroGeneral Cabal | 0 - 2 | CearaCeara |
| 27 Apr 22 | r03 | Everton de Viña del MarEverton de Vi | 2 - 1 | Ayacucho FCAyacucho FC |
| 27 Apr 22 | r03 | Independiente MedellínIndependiente | 0 - 1 | InternacionalInternacional |
| 27 Apr 22 | r03 | FluminenseFluminense | 0 - 0 | UnionUnion |
| 27 Apr 22 | r03 | FBC MelgarFBC Melgar | 3 - 1 | Racing ClubRacing Club |
| 27 Apr 22 | r03 | CuiabaCuiaba | 1 - 2 | CA River PlateCA River Plat |
| 27 Apr 22 | r03 | Guaireña FCGuaireña FC | 1 - 0 | 9 de Octubre9 de Octubre |
| 28 Apr 22 | r03 | Universidad Católica del Universidad C | 2 - 0 | BanfieldBanfield |
| 28 Apr 22 | r03 | Deportes AntofagastaDeportes Anto | 2 - 1 | Atletico GOAtletico GO |
| 28 Apr 22 | r03 | WilstermannWilstermann | 1 - 3 | Sao PauloSao Paulo |
| 28 Apr 22 | r03 | Defensa y JusticiaDefensa y Jus | 1 - 2 | LDU QuitoLDU Quito |
| 29 Apr 22 | r03 | WanderersWanderers | 0 - 1 | LanusLanus |
| 29 Apr 22 | r03 | Barcelona SCBarcelona SC | 1 - 0 | Metropolitanos F.C.Metropolitano |
| 29 Apr 22 | r03 | Unión La CaleraUnión La Cale | 1 - 1 | Santos FCSantos FC |
| 29 Apr 22 | r03 | Oriente PetroleroOriente Petro | 1 - 3 | Atlético JuniorAtlético Juni |
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