[2] The draw for the second stage was held on 4 June 2018, 20:00 PYT (UTC−4), at the CONMEBOL Convention Centre in Luque, Paraguay.
If still tied, extra time would not be played, and the penalty shoot-out would be used to determine the winner (Regulations Article 27).
Tied 1–1 on aggregate, Colón won on penalties and advanced to the round of 16 (Match D).
Tied 4–4 on aggregate, Deportivo Cuenca won on penalties and advanced to the round of 16 (Match F).
Tied 1–1 on aggregate, Junior won on penalties and advanced to the round of 16 (Match D).