Brazil's Atletico PR and Argentine outfit Velez will meet at the Estadio Durival de Brito e Silva on Wednesday, with both sides locked on nine points and plus-three goal difference.
The tightness of the top three in the group is bound to leave one side unlucky, and despite three wins from four matches, neither side is assured of progression with a win.
Miguel Portugal's men should be heavily favoured in Curitiba, where they have not lost in continental competition in their past seven matches.
The Strongest are on the road at Peru's Universitario on Thursday, and the Bolivian club can continue to heap the pressure on the top two in Group One with victory over the cellar-dwellers.
Eduardo Villegas' men from La Paz have six points with two games to play, and if they enforce a fifth straight loss on Universitario in this competition, they will have their fate in their own hands come the final matchday.
In Group Two, bottom sides Independiente del Valle and San Lorenzo (both four points) will go head-to-head in a virtual elimination battle on Thursday.
Ecuador's Independiente are at home and a win over their Argentine counterparts would significantly boost their chances of reeling in Botafogo (seven) and Union Espanola (six), who play their next fixture in April.
Also on Thursday, top plays bottom in Group Three as Argentina's Lanus (four points) tackle Paraguayan club Cerro Porteno (seven).
In other Wednesday fixtures, Colombia's Deportivo Cali welcome Chilean outfit O'Higgins in a crucial Group Three tie, while Leon of Mexico can seal progression to the knockout stages with a win at home to Bolivian side Bolivar, Venezuela's Deportivo Anzoategui host Arsenal of Argentina and another Argentine outfit Newell's Old Boys will travel to Uruguay to play Nacional.
Zamora will begin the week's Copa Libertadores action on Tuesday when they welcome Paraguayan club Nacional Asuncion to Venezuela, while Mexico's Santos Laguna will face Penarol of Uruguay.
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