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Results
Third Round
7 April 2021 - 16 April 2021
Results - - Third Round 2021
Junior Barranquilla (COL) | 4 - 2 |  Club Bolívar (BOL) | ||
| 09/04/2021 - 02h30 | Club Bolívar (BOL) | 2 - 1 | Junior Barranquilla (COL) | |
| 16/04/2021 - 02h30 | Junior Barranquilla (COL) | 3 - 0 | Club Bolívar (BOL) |
San Lorenzo de Almagro (ARG) | 3 - 5 |  Santos FC (BRA) | ||
| 07/04/2021 - 02h30 | San Lorenzo de Almagro (ARG) | 1 - 3 | Santos FC (BRA) | |
| 14/04/2021 - 02h30 | Santos FC (BRA) | 2 - 2 | San Lorenzo de Almagro (ARG) |
Independiente José Terán (ECU) | 4 - 2 |  Grêmio Porto Alegre (BRA) | ||
| 10/04/2021 - 00h15 | Independiente José Terán (ECU) | 2 - 1 | Grêmio Porto Alegre (BRA) | |
| 15/04/2021 - 00h15 | Grêmio Porto Alegre (BRA) | 1 - 2 | Independiente José Terán (ECU) |
Club Libertad (PAR) | 2 - 4 |  Atlético Nacional Medellín (COL) | ||
| 08/04/2021 - 02h30 | Club Libertad (PAR) | 1 - 0 | Atlético Nacional Medellín (COL) | |
| 15/04/2021 - 02h30 | Atlético Nacional Medellín (COL) | 4 - 1 | Club Libertad (PAR) |
Peñarol
CA Independiente