Meanwhile, the away side make the journey to Santa Fe also looking to pick up all three points for the first time this term.
Match preview
River Plate were left to rue their luck in a 0-0 stalemate against Atletico Tucuman at the Estadio Antonio Vespucio Liberti on Sunday.
Marcelo Gallardo's men dominated the game but failed to find the breakthrough as they ran into an inspired opposition goalkeeper on the day.
Off the back of what has been a slow start to the new campaign, Los Millonarios sit 21st in the league table with just two points from their opening two matches.
Awaiting the Buenos Aires-based outfit next is a clash versus an opposing side aiming to exact revenge for a 4-0 defeat in the most recent encounter between the teams.
Having lost just two of their last 22 games on the road across all competitions, Wednesday's visitors will be confident of picking up another positive result away from home.
Colon had to settle for a second consecutive share of the spoils on home turf following a 2-2 draw against city rivals Union de Santa Fe in a thrilling derby on Sunday.
Julio Cesar Falcioni's men went behind to Mauro Luna Diale's strike before turning the game on its head thanks to strikes from Facundo Farias and Ramon Abila, only for Jonathan Alvez to score a late equaliser from the penalty spot.
Consequently, El Sabalero have amassed just two points so far and are in 15th place as things stand, level on points with their next opponents
Unbeaten in each of their last six home games against Wednesday's visitors, the hosts have proven themselves to be a tough nut to crack and will set out to continue in the same vein.
Colon Argentine Primera Division form:
Colon form (all competitions):
River Plate Argentine Primera Division form:
River Plate form (all competitions):
Team News
Juan Quintero is set to miss a 12th game on the bounce as the River Plate midfielder continues to battle with a knee problem.
Robert Rojas also misses out through a torn muscle which he picked up in a Copa Libertadores group-stage clash against Allianz Lima back in April.
Colon are set to be without the services of the Argentinian duo of Paolo Goltz and Cristian Vega who are both nursing knee injuries.
Jonathan Sandoval is a major doubt for the game with the 34-year-old looking to shake off a slight knock just in time to feature on Wednesday.
Facundo Garces will serve a one-match suspension in this one after receiving his marching orders for two bookable offences last time out.
Colon possible starting lineup:
Burian; Delgado, Novillo, Meza, Acevedo; Lertota, Bernardi, Aliendro; Farias, Teuten, Abila
River Plate possible starting lineup:
Armani; Herrera, Maidana, Gonzalez, Gomez; Perez, Fernandez, Palavecino; Barco, Simon, Alvarez