| 05 Apr 22 | r01     | Caracas F.C.Caracas F.C. | 0 - 0 | Atletico PRAtletico PR |
| 05 Apr 22 | r01 | Club OlimpiaClub Olimpia | 0 - 0 | Cerro PorteñoCerro Porteño |
| 05 Apr 22 | r01 | ColonColon | 2 - 1 | PeñarolPeñarol |
| 06 Apr 22 | r01 | Always ReadyAlways Ready | 2 - 0 | CorinthiansCorinthians |
| 06 Apr 22 | r01 | Deportivo CaliDeportivo Cal | 2 - 0 | Boca JuniorsBoca Juniors |
| 06 Apr 22 | r01 | Sporting CristalSporting Cris | 0 - 2 | FlamengoFlamengo |
| 06 Apr 22 | r01 | BragantinoBragantino | 2 - 0 | Nacional MontevideoNacional Mont |
| 06 Apr 22 | r01 | America MGAmerica MG | 0 - 2 | Independiente del ValleIndependiente |
| 06 Apr 22 | r01 | Talleres de CordobaTalleres de C | 1 - 0 | Universidad CatólicaUniversidad C |
| 07 Apr 22 | r01 | Deportivo Táchira F.C.Deportivo Tác | 0 - 4 | PalmeirasPalmeiras |
| 07 Apr 22 | r01 | Deportes TolimaDeportes Toli | 0 - 2 | Atletico MGAtletico MG |
| 07 Apr 22 | r01 | Alianza LimaAlianza Lima | 0 - 1 | River PlateRiver Plate |
| 07 Apr 22 | r01 | Independiente PetroleroIndependiente | 1 - 1 | EmelecEmelec |
| 07 Apr 22 | r01 | FortalezaFortaleza | 1 - 2 | Colo-ColoColo-Colo |
| 08 Apr 22 | r01 | Estudiantes de la PlataEstudiantes d | 4 - 1 | Velez SarsfieldVelez Sarsfie |
| 08 Apr 22 | r01 | The StrongestThe Strongest | 1 - 1 | Club LibertadClub Libertad |
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