Both teams have claimed two wins from as many games in their groups and a third – halfway through the stage – would set them up nicely.
Mineiro have edged their way to the top of Group 4 and sit three points clear of Santa Fe and Nacional Asuncion ahead of their clash against the Paraguayans on Wednesday.
Paulo Autuori's Mineiro are on a seven-match unbeaten run in all competitions and have been scoring for fun.
The Brazilians have netted 16 goals in their past five matches, sharing the load up front.
Neto Berola has struck twice in his past three outings, including the winning goal in the 2-1 win over Santa Fe in February.
Colombia's Santa Fe need to bounce back from that loss when they travel to Venezuela to take on Zamora, who are bottom of Group 4.
Velez Sarsfield are setting the pace in Group 1 ahead of their clash against The Strongest on Tuesday.
The Argentines are yet to concede in two matches and a win in Bolivia would set them up nicely for a place in the round of 16.
The clash between the top two shapes as an opportunity for Atletico Paranaense and Universitario to close in, with the former going into second with a win if The Strongest fail to claim victory.
Group 2 is even heading into matchday three, but leaders Botafogo have an opportunity to edge further than a point clear when they visit lowly Ecuadorians Independiente del Valle.
San Lorenzo and Union Espanola do battle in Argentina in the other match.
In Group 3, the top two of O'Higgins and Cerro Porteno meet, while Deportivo Cali host Lanus on Thursday.
Undoubtedly the most even group, teams in Group 5 will be hoping to settle into the top two.
Cruzeiro visit Defensor Sporting and Real Garcilaso host Universidad Chile with all four teams locked on three points.
Gremio lead Group 6 by three points ahead of their clash at home to Newell's Old Boys, while Nacional desperately need a win when they visit Atletico Nacional.
In Group 7, Leon visit Emelec and Flamengo host Bolivar with all four teams very much alive in the battle for qualification.
Santos Laguna will be aiming to make it three from three in Group 8 when they visit Deportivo Anzoategui, while Arsenal host Penarol.
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