| 03 May 22 | r04     | Deportivo Táchira F.C.Deportivo Tác | 1 - 4 | EmelecEmelec |
| 03 May 22 | r04 | Caracas F.C.Caracas F.C. | 1 - 0 | Club LibertadClub Libertad |
| 03 May 22 | r04 | The StrongestThe Strongest | 5 - 0 | Atletico PRAtletico PR |
| 04 May 22 | r04 | Independiente PetroleroIndependiente | 0 - 5 | PalmeirasPalmeiras |
| 04 May 22 | r04 | Estudiantes de la PlataEstudiantes d | 1 - 0 | Nacional MontevideoNacional Mont |
| 04 May 22 | r04 | America MGAmerica MG | 1 - 2 | Atletico MGAtletico MG |
| 04 May 22 | r04 | ColonColon | 2 - 1 | Cerro PorteñoCerro Porteño |
| 04 May 22 | r04 | Talleres de CordobaTalleres de C | 2 - 2 | FlamengoFlamengo |
| 05 May 22 | r04 | Deportivo CaliDeportivo Cal | 0 - 0 | CorinthiansCorinthians |
| 05 May 22 | r04 | Always ReadyAlways Ready | 0 - 1 | Boca JuniorsBoca Juniors |
| 05 May 22 | r04 | Club OlimpiaClub Olimpia | 1 - 0 | PeñarolPeñarol |
| 05 May 22 | r04 | Deportes TolimaDeportes Toli | 1 - 0 | Independiente del ValleIndependiente |
| 05 May 22 | r04 | Sporting CristalSporting Cris | 1 - 1 | Universidad CatólicaUniversidad C |
| 05 May 22 | r04 | FortalezaFortaleza | 1 - 1 | River PlateRiver Plate |
| 06 May 22 | r04 | BragantinoBragantino | 1 - 1 | Velez SarsfieldVelez Sarsfie |
| 06 May 22 | r04 | Alianza LimaAlianza Lima | 1 - 1 | Colo-ColoColo-Colo |
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