Leaders Botafogo can move a step closer to qualification from Copa Libertadores' Group 2 when they play host to rivals Union Espanola.
Botafogo, Brazil's Campeonato Carioca champions in 2013, and Chilean outfit Union Espanola will meet at the Estadio Jornalista Mario Filho on Wednesday with just one point separating both teams after four matchdays.
Eduardo Hungaro's men have collected seven points from their opening four games, while Union Espanola have six points thus far.
Although both teams are not assured progression, with Independiente del Valle (five) and San Lorenzo (five) still in with a shout.
Botafogo are unbeaten at home in the Copa Libertadores this season but their recent run of form in all competitions has Union Espanola full of confidence heading into matchday five.
The Brazilian outfit edged Independiente del Valle two weeks ago but that is the team's only win in eight previous outings, while Union Espanola have tasted defeat just once in their last eight games.
In Group 5, leaders Universidad de Chile welcome Cruzeiro to the Estadio Nacional Julio Martinez Pradanos on Thursday.
Universidad de Chile have won two consecutive games since they were trounced 5-1 by Cruzeiro on matchday two.
Ricardo Goulart starred with a hat-trick that day and Universidad de Chile will be out to avoid a repeat of that disastrous performance.
Uruguay's Defensor Sporting can close the gap on their Chilean opponents when they play host to Peruvian outfit Real Garcilaso, who sit bottom of the group, on Tuesday.
In Group 4, cellar dwellers Santa Fe face an uphill task when Brazilian giants Atletico Mineiro visit Colombia on Thursday.
Since losing to Mineiro on the opening matchday, Santa Fe have lost and drawn to Venezuela's Zamora in reverse fixtures to fall three points adrift of the qualifying spots.
Ecuador Primera A leaders Emelec will be aiming to bounce back from their league defeat to El Nacional when they go head-to-head against Brazil's Flamengo in Group 7 action on Wednesday.
Meanwhile, Brazilian club Gremio can leapfrog Newell's Old Boys into top spot in Group 6 with victory over Atletico Nacional of Colombia on Wednesday.