Nacional are in danger of missing the Copa Libertadores group stage for the first time since 1996 as they prepare to host Oriente Petrolero.
In last week s first round first leg, a blistering strike from Gualberto Mojica gave Oriente a 1-0 victory at home in Bolivia.
Oriente will head to Montevideo on Tuesday knowing a 2-1 loss would be enough for them to advance at the expense of Nacional.
It would be a huge shock for Nacional perennial challengers for South America s premier continental club competition.
Nacional have won the Copa Libertadores three times (1971, 1980, 1988), while they made the semi-finals as recently as 2009, but having qualified as Uruguay s third-best team this year, they were forced into a play-off to earn a spot in the group stage.
In their favour will be a strong crowd at the Estadio Gran Parque Central in Montevideo, while they have warmed up with a 2-0 triumph over local rivals Racing on Saturday in their opening match of the Uruguayan Primera Division s Clausura championship.
Coach Gerardo Pelusso was still able to rest key players such as Richard Porta, Ivan Alonso and Pablo Alvarez.
Porta will be one of Pelusso s main weapons up front against Oriente, while Nacional can also call upon the impressive talents of veteran playmaker Alvaro Recoba with the former Inter man still a handy option off the bench with his wicked left foot.
Argentina s Lanus are in the best position to advance of the 12 teams involved in the Copa Libertadores first round.
The reigning Copa Sudamericana champions won 2-0 over Caracas in Venezuela thanks to a brace from Paolo Goltz.
In all the other ties, just a single goal separates the two teams.
Colombia s Santa Fe and Atletico Paranaense of Brazil will head home with some confidence after managing away goals in their respective 2-1 losses to Liga MX outfit Morelia and Sporting Cristal of Peru.
Ecuador s Deportivo Quito must travel to Brazil with a 1-0 advantage over Botafogo, while Chile s Universidad de Chile is in the same position ahead of their trip to Paraguay to play Guarani.