In last week's quarter-final first leg between Nacional and Defensor in Colombia, the Uruguayan visitors won 2-0 with late goals from Leonardo Pais and Nicolas Olivera.
The victory puts Defensor in the box seat for a spot in the Copa Libertadores' final four - with the Montevideo-based club having never gone further than the quarter-finals in the continental competition.
But Defensor head coach Fernando Curutchet would have been disappointed by his team's effort in the lead-up to Thursday's second leg, as they lost 2-1 to Wanderers in the Uruguayan Primera Division on Sunday.
Olivera and Brazilian winger Felipe Gedoz will be crucial to Curutchet's game plan, as the pair of wingers are Defensor's leading scorers in the Copa Libertadores this season with four each.
In the other quarter-final second leg on Thursday, Bolivar will hope to ride the momentum of last week's stoppage-time equaliser to overcome Lanus.
In the quarter-final second legs scheduled for Wednesday, Argentina's Arsenal will host Nacional Asuncion, after the latter won the first leg 1-0 in Paraguay, while Cruzeiro will welcome San Lorenzo to Brazil.
