Both sides will be looking to register their first win in this year's tournament, with Deportivo drawing their first two while the Colombian side have suffered a couple of defeats.
Match preview
Despite having only 28% and 32% possession in their opening two games in this year's Copa Libertadores, and conceding 29 and 16 shots against Atletico Mineiro and Cerro Porteno respectively, Deportivo have managed to pick up two draws so far.
The Venezuelan side opened the scoring through defender Luis Martinez in their opening tie in the competition against the Brazilian outfit, before conceding a second-half goal to end the tie 1-1.
Deportivo were unable to register a shot against Cerro Porteno, as they held the Paraguayan champions to a goalless draw away from home last week.
Following 0-0 draws in their opening two games in their domestic season, Los Naranjas managed to record a 2-0 win away to Yaracuyanos through first-half goals from Aquiles Ocanto and Ronaldo Lucena.
It should be no surprise that they have kept four clean sheets in their opening five in all competitions this season as their manager Daniel Farias was a goalkeeper during his playing days, with a solid defence being a pivotal reason in them winning their first Venezuelan league title in 2020.
Meanwhile, America de Cali are in desperate need of a win on Friday, otherwise they will be set for an early exit from the Copa Libertadores after losing their opening two games 2-0 and 2-1.
In their first game at home to Cerro Porteno, America dominated possession but failed to create any clear-cut chances, testing the opposition goalkeeper on only two occasions in the entire match.
A second-half brace for Hulk put Atletico Mineiro 2-0 up in last week's game, with substitute Luis Sanchez's goal proving to be a consolation.
Having won the Colombian title last season, Francisco Arce's side have also been in poor form in the league this year winning one of their last five games and dropping down to eighth after 18 games.
Deportivo La Guaira Copa Libertadores form:
Deportivo La Guaira form (all competitions):
America de Cali Copa Libertadores form:
America de Cali form (all competitions):
Team News
Farias made eight changes to his starting lineup on Sunday following their previous match against Cerro Porteno and he is likely to rotate back to his strongest team ahead of Friday's clash, despite winning 2-0 on the weekend.
Goalkeeper Carlos Olses will certainly start after registering four clean sheets out of five this season and will likely be joined by forward Ocanto after scoring last time out.
The away side will yet again be without forward Adrian Ramos, who is out injured, but Steven Lucumi has fully recovered from his injury and could possibly start after coming on for 30 minutes on Sunday.
Despite being suspended in the domestic competition following his straight red card two games ago, Yesus Cabrera is eligible and likely to start in Friday's Copa Libertadores clash.
Deportivo La Guaira possible starting lineup:
Olses; Flores, Martinez, La Mantia, Mejias, Cumana; Pena, Flores, Lucena; Reyes, Ocanto
America de Cali possible starting lineup:
Graterol; Arrieta, Torres, Murillo, Cabezas; Carrascal, Urena, Cabrera; Moreno, Rodriguez, Vergara
We say: Deportivo La Guaira 1-0 America de Cali
America have been in poor form of late, while Deportivo are unbeaten in all competitions this season. The Venezuelan side are very solid at the back and are likely to keep another clean sheet this Friday yet have struggled to score many goals this season, meaning it is likely to be a very low scoring affair.