The hosts open the scoreline against Santos thanks to Sebastian Ferreira's goal and level the series at 2-2 on aggregate, with the Paraguayans ahead on away goals.
Peñarol defeat Sporting Cristal to advance to the semifinals of the Copa Sudamericana.
Despite losing, Peñarol did enough to eliminate Nacional to advance to the quarterfinals of the Copa Sudamericana.
Emiliano Vecchio scored the only goal of the game to help Rosario Central eliminate Deportivo Tachira in the Copa Sudamericana.
Guzman Corujo scores a late consolation goal to make it 1-0 to Nacional over Peñarol.
Santos hold on to eliminate Independiente and advance to the quarterfinals of the Copa Sudamericana.