The hosts were defeated by Braga in the Taca da Liga semi-finals, while the visitors lost 3-1 to Vitoria de Guimaraes.
Jorge Jesus has been coming under some pressure at the Estadio da Luz in recent weeks after his side fell four points behind city-rivals Sporting Lisbon in the league standings before being dumped out of the League Cup by Braga.
The Eagles finished runners-up last season and are desperate to return to the summit of Portuguese football this time around.
Despite their recent woes in the cup competitions, Benfica are currently on a seven-game unbeaten run in the Primeira Liga.
With Sporting not playing until Tuesday, this upcoming encounter is the perfect opportunity for Jesus's men to pile the pressure on the Verde e Brancos and move to within a point of the league leaders.
Benfica will see this as a great opportunity to regain their rhythm and momentum given Nacional's lowly status in the league table.
Luis Freire's side are on a four-game losing streak at this moment in time and are in danger of being dragged into the relegation zone.
The Estadio da Madeira outfit are 14th in the Primeira Liga standings after picking up just 13 points from their opening 14 games and are just one point above the bottom three.
Scoring goals has been Nacional's issue this campaign. They have found the back of the net on just 12 occasions throughout 2020-21 and have their relatively solid defence to thank for what success they have had so far.
Freire will know his side will not face many bigger tasks than coming up against the 37-time Portuguese champions away from home and will be seeing this clash as a free hit where they have nothing to lose.
Benfica Primeira Liga form: WWWDWD
Benfica form (all competitions): WDWWDL
Nacional Primeira Liga form: LLWLLL
Nacional form (all competitions): WWLLLL
Benfica have been heavily affected by an outbreak of coronavirus within the club, which has seen several first-team players return positive test results.
Nacional are one of the few Portuguese clubs that have managed to avoid any coronavirus cases, but they do have several injuries and suspensions to contend with.
Benfica possible starting lineup:
Vlachodimos; Jardel, Weigl, Todibo; Cervi, Pizzi, Taarabt, Silva, Ferreira; Nunez, Seferovic
Nacional possible starting lineup:
Guimaraes; Vigario, Kal, Henrique, Souza; Borges; Gorre, Azouni, Ramos, Camacho; Riascos
We say: Benfica 2-0 Nacional
Although Benfica have a seriously depleted squad for this upcoming encounter, they should have far too much quality for a struggling Nacional squad. The likes of Haris Seferovic and Darwin Nunez will still be available and, with the firepower on display for the capital club, we fancy them to secure the three points.