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.
Nacional will have to do without playmaker Edwin Cardona in Montevideo, after the 21-year-old was red-carded with four minutes remaining in the first leg but the Colombian club should be fresh, as they did not play in their domestic league over the weekend.
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.
Bolivar captain William Ferreira struck a stunning long-range goal in the first minute of stoppage time in Argentina to claim a 1-1 draw at Lanus in the first leg.
Both Bolivar and Lanus lost in the league over the weekend but the latter will surely travel from Argentina to Bolivia deflated after giving up a lead in the opening leg of the tie.
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.
San Lorenzo won the first leg in Argentina 1-0.
