| 12 Apr 22 | r02     | Boca JuniorsBoca Juniors | 2 - 0 | Always ReadyAlways Ready |
| 12 Apr 22 | r02 | Cerro PorteñoCerro Porteño | 3 - 1 | ColonColon |
| 12 Apr 22 | r02 | Universidad CatólicaUniversidad C | 2 - 1 | Sporting CristalSporting Cris |
| 13 Apr 22 | r02 | PalmeirasPalmeiras | 8 - 1 | Independiente PetroleroIndependiente |
| 13 Apr 22 | r02 | PeñarolPeñarol | 2 - 1 | Club OlimpiaClub Olimpia |
| 13 Apr 22 | r02 | FlamengoFlamengo | 3 - 1 | Talleres de CordobaTalleres de C |
| 13 Apr 22 | r02 | Club LibertadClub Libertad | 2 - 1 | Caracas F.C.Caracas F.C. |
| 13 Apr 22 | r02 | Colo-ColoColo-Colo | 2 - 1 | Alianza LimaAlianza Lima |
| 14 Apr 22 | r02 | River PlateRiver Plate | 2 - 0 | FortalezaFortaleza |
| 14 Apr 22 | r02 | Nacional MontevideoNacional Mont | 0 - 0 | Estudiantes de la PlataEstudiantes d |
| 14 Apr 22 | r02 | Atletico MGAtletico MG | 1 - 1 | America MGAmerica MG |
| 14 Apr 22 | r02 | CorinthiansCorinthians | 1 - 0 | Deportivo CaliDeportivo Cal |
| 14 Apr 22 | r02 | Independiente del ValleIndependiente | 2 - 2 | Deportes TolimaDeportes Toli |
| 14 Apr 22 | r02 | Atletico PRAtletico PR | 1 - 0 | The StrongestThe Strongest |
| 15 Apr 22 | r02 | Velez SarsfieldVelez Sarsfie | 2 - 2 | BragantinoBragantino |
| 15 Apr 22 | r02 | EmelecEmelec | 1 - 1 | Deportivo Táchira F.C.Deportivo Tác |
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