Both teams head into this one off the back of victories in their last outings and will be looking to pick up where they left off.
Match preview
Nacional eased past the challenge of Defensor Sporting in a routine 2-0 win at the Estadio Luis Franzini on Saturday.
Goals in either half from Emanuel Gigliotti and Camilo Candido secured a well-deserved three points for Pablo Repetto's men on the club's 123rd anniversary.
The Tricolors now sit second in the Apertura Premier Division, but their form in this season's Copa Libertadores has left a lot to be desired.
Off the back of a 1-0 defeat versus Estudiantes in matchday four, the Uruguayan outfit are third in Group C having managed just four points so far.
Going up against an opposing side who are yet to come out on top in any of the previous meetings between the teams, Wednesday's hosts will fancy themselves to get the job done and breathe life back into their continental campaign.
Velez Sarsfield saw off the threat of Santa Fe in a 2-1 victory on Monday to make it back-to-back league wins in the Argentine top flight.
Abel Osorio and Lucas Janson were on target for Julio Vaccari's men either side of Ramon Abila's strike at the Estadio B.G. Estanislao Lopez.
Sitting bottom of Group C with just two points heading into their fifth group-stage fixture, El Fortin will be keen to come away with all three points in order to preserve their chances of reaching the knockout phase of the Copa Libertadores for the second year running.
Off the back of ending a 12-game winless streak on the road last time out, Wednesday's visitors set out to record what could potentially be a season-defining victory away from home.
Nacional Copa Libertadores form:
Nacional form (all competitions):
Velez Sarsfield Copa Libertadores form:
Velez Sarsfield form (all competitions):
Team News
Nacional's Emanuel Gigliotti has scored three goals in his last four appearances, including a double in the reverse fixture, and the forward is one to keep an eye on.
Alex Castro will be pushing for a place in the XI here after he made his return to action against Defensor Sporting last time out.
Meanwhile, Manuel Monzeglio is a doubt for the home side having come off with an injury in the aforementioned game.
Jose Florentin missed Velez's trip to Bragantino in round four due to a suspension, but the Paraguayan is now eligible to feature once again.
Nineteen-year-old Abel Osorio found the back of the net in his first start for over a year, which could see him retain a starting spot in this one.
Nacional possible starting lineup:
Rochet; Candido, Marichal, Leo Coelho, J. Rodriguez; Carballo, Y. Rodriguez; Castro, Trezza, Zabala; Gigliotti
Velez Sarsfield possible starting lineup:
Hoyos; Ortega, Gomez, Matias, Guidara; Garayalde, Perrone; Janson, Sonora, Fernandez; Osorio