| 25 May 21 | r06     | PalestinoPalestino | 1 - 2 | Club LibertadClub Libertad |
| 25 May 21 | r06 | Newells Old BoysNewells Old B | 1 - 1 | Atletico GOAtletico GO |
| 26 May 21 | r06 | EmelecEmelec | 1 - 4 | Talleres de CordobaTalleres de C |
| 26 May 21 | r06 | Deportes TolimaDeportes Toli | 1 - 2 | BragantinoBragantino |
| 26 May 21 | r06 | IndependienteIndependiente | 1 - 0 | Club Deportivo GuabiráClub Deportiv |
| 26 May 21 | r06 | BahiaBahia | 2 - 4 | Montevideo City TorqueMontevideo Ci |
| 27 May 21 | r06 | Rosario CentralRosario Centr | 0 - 0 | 12 de Octubre12 de Octubre |
| 27 May 21 | r06 | HuachipatoHuachipato | 0 - 3 | San LorenzoSan Lorenzo |
| 27 May 21 | r06 | CorinthiansCorinthians | 4 - 0 | Club River Plate AsunciónClub River Pl |
| 27 May 21 | r06 | Sport HuancayoSport Huancay | 0 - 0 | PeñarolPeñarol |
| 27 May 21 | r06 | WilstermannWilstermann | 1 - 0 | CearaCeara |
| 27 May 21 | r06 | Arsenal SarandiArsenal Saran | 3 - 1 | BolivarBolivar |
| 28 May 21 | r06 | Atletico PRAtletico PR | 4 - 0 | SD AucasSD Aucas |
| 28 May 21 | r06 | FBC MelgarFBC Melgar | 0 - 0 | Metropolitanos F.C.Metropolitano |
| 28 May 21 | r06 | LanusLanus | 0 - 0 | Aragua F.C.Aragua F.C. |
| 28 May 21 | r06 | La EquidadLa Equidad | 0 - 0 | GremioGremio |
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