The Brazilian club defeated Tigre in last year's final, having beaten Chilean opposition 5-0 at the last-eight stage before also seeing off Catolica in the semi-finals.
However, Muricy Ramalho's men must travel for the second leg, and so will hope to build up a convincing lead at Morumbi when the tie gets under way.
Two-time Copa Libertadores winners River Plate are another illustrious club to have reached the quarter-finals this year, and they will take on LDU Loja of Ecuador there.
But Brazil are by far the best-represented nation at this stage of the competition, with a further four clubs from the country having made it through the first and second stages.
Coritiba and Ponte Preta both begin the quarters with home clashes, as they take on Colombian opposition in the form of Itagui and Deportivo Pasto respectively.
Bahia also face a team from Colombia in Atletico Nacional, though they will need to travel for the first leg, as will Sport Recife when they face Libertad of Paraguay.
Elsewhere, the two other remaining Argentine teams - Lanus and Velez Sarsfield - play Universidad Chile and La Equidad of Colombia respectively.
