Through their first four games of the group stage, the Chileans are in second place with six points, while their opponents need to win their last two matches and likely get some help to continue their journey towards South American glory.
Match preview
Universidad may have started the group stage poorly, but Decano have had a rough round-robin, earning just two points in their opening four fixtures.
Their work defensively has delivered them two consecutive Uruguayan Primera titles, conceding fewer than 20 goals in each round of their 2019 and 2020 triumphs.
So far in this competition, their rugged defence appears to have fallen asleep, conceding nine goals up to this point.
In attack, they have been relying almost exclusively on their strikers Leandro Fernandez and Gonzalo Bergessio.
Together, they have scored all five goals for Nacional in the competition so far, with Bergessio netting a hat-trick in a thrilling 4-4 draw with Atletico Nacional.
Manager Alejandro Capuccio has seen his team chasing most of their games in the group stage, as they have had the ball less than 40% of the time in two of their previous outings.
After topping their group in 2020, it would be a disappointment if they missed a chance to make the second round of this competition while also losing a spot in the Copa Sudamericana, given to all third-place finishers in the group stage.
With two games remaining, the defending Primera Division champions in Chile now represent the country's best hope of ending a lengthy drought in this tournament.
Only one Chilean side has ever captured this famous trophy, but it has been quite some time since Colo-Colo won this competition in 1991.
Considered one of 'The Big Three' clubs in Chile, La Catolica will be determined to not finish as the number three team in their group for a third consecutive season in this competition.
So far, their 2021 group stage form has been virtually a carbon copy of the one we saw from them in the previous season, where they lost their first two games each time before recovering, but in the end, coming up just short of a second-round berth.
The good news for manager Gus Poyet and his team is that their 2021 group stage story has yet to be written entirely, and they have a chance to change their fate by winning their final two games in this group.
On Tuesday, a win in Uruguay would bury many bad memories for the Chileans, who have never beaten Nacional on their home turf in their eight previous visits in this competition.
Nacional Copa Libertadores form:
Nacional form (all competitions):
Universidad Catolica Copa Libertadores form:
Universidad Catolica form (all competitions):
Team News
Sergio Rochet picked up his first clean sheet in this competition in his last match against a team with a lot of scoring depth in Atletico Nacional.
He is expected to start once again with Guillermo Centurion out with COVID symptoms.
A lack of discipline at this point of the tournament will cost the Uruguayans heading into this match.
Christian Almeida, Camilo Candido and Felipe Carballo will all miss this big game due to red card suspensions.
Universidad remain without German Lanaro, who has a ruptured cruciate ligament, while Gonzalo Tapia is out with a torn muscle, and Diego Buonanotte has an abductor problem.
Striker Edson Puch is suspended for Catolica after getting a straight red card just six minutes after his side scored the winning goals against Argentinos Juniors.
After leading the team in goals domestically this past season, Diego Valencia has been quiet so far in this competition with just one goal in their 3-1 win against Nacional on Matchday three.
Nacional possible starting lineup:
Rochet; Oliveros, Corujo, Marichal, Laborda; Vega, Neves, Trasante, Ocampo; Fernandez, Bergessio
Universidad Catolica possible starting lineup:
Dituro; Rebolledo, Astaburuaga, Huerta, Parot; Nunez, Silva, Leiva; Montes, Zampedri, Fuenzalida
We say: Nacional 1-2 Universidad Catolica
Universidad are in fine form at the moment with three wins while also maintaining two shutouts for veteran goalkeeper Matias Dituro.
Nacional do not look like the same team that won their qualifying group a season ago and have lacked discipline with three red cards in their past three games in this competition.