Meanwhile, the home side are simply aiming to restore some respectability after losing all five of their group-stage matches.
Match preview
Sitting down in 19th position in the Brazilian top flight, it is fair to say that America Mineiro have endured a dismal campaign on the domestic front.
However, despite collecting just one point and conceding seven goals in three matches, they remain optimistic that they can still progress in the Copa Sudamericana.
A 2-0 victory over Millonarios has kept Vagner Mancini's team in the hunt for a top-two spot, that result keeping them to within three points of the second-placed side.
With frontrunners Defensa y Justicia playing host to Millonarios in their final game, there is a plausible scenario where a win will be enough for America Mineiro.
Something not in their favour is their record away from home, Coehlo having failed to prevail on their travels since the middle of April.
From Penarol's perspective, they head into this fixture simply looking for a confidence boost as they currently on a six-match winless streak.
A goalless draw at Montevideo Wanderers in the Uruguayan top flight last time out was a step in the right direction, but this is a team that has not tasted success since May 9.
Decano are now without a manger as they bid to get back on track, and they will want to avoid losing each of their encounters at this stage of the competition.
Since they posted a stunning 4-0 triumph at River Plate in March, they have shipped 16 goals in just five games, only conceding no more than twice on one occasion.
Penarol Copa Sudamericana form:
W
L
L
L
L
L
Penarol form (all competitions):
D
L
L
L
L
D
America Mineiro Copa Sudamericana form:
W
L
D
L
W
America Mineiro form (all competitions):
W
W
W
D
L
L
Team News
Penarol caretaker boss Juan Manuel Olivera must decide whether to stick with the players that restored some belief in keeping a clean sheet at Montevideo.
In comparison to the last side that played in this competition, players such as Joaquin Ferreira, Lucas Hernandez and Brian Mansilla would receive chances from the flanks if he takes that approach.
Meanwhile, America Mineiro boss Mancini may see no reason to make any alterations with their defeat to Internacional stemming from changes made after the hour mark.
Emmanuel Martinez may be brought back into the side in attacking-midfield, possibly replacing youngster Breno Cascardo.
Penarol possible starting lineup:
Cardozo; Ferreira, Menosse, Leo Coehlo, L.Hernandez; Mansilla, Garcia, Cristotoro, Mendez; A.Hernandez, Arezo
America Mineiro possible starting lineup:
Cavichioli; Marcinho, Wanderson, Iago Maidana, Avelar; Martinez, Kal, Juninho; Everaldo, Aloisio, Azevedo
We say: Penarol 2-3 America Mineiro
With these teams facing contrasting levels of pressure, we would not be surprised to see the home side push their opponents all the way. However, we cannot ignore that the visitors must go on the offensive, leading us to predict an away victory in a five-goal thriller.