Ruben Amorim's men picked up an important victory over fourth-placed Braga last time out, while Nacional kept their survival hopes alive with a 1-0 win over Vitoria de Guimaraes, breaking a 10-game losing run in the Portuguese top flight.
Sporting Lisbon made an important return to winning ways last time out, as they hosted fourth-placed Braga after a slightly inconsistent spell in the league.
The odds looked to be stacked against the league leaders when centre-back Goncalo Inacio was shown a red card after 18 minutes, but Amorim's side would withstand intense pressure and go on to snatch a late winner through Matheus Nunes in the 81st minute.
While they were by no means the better side in that game, Amorim will definitely be encouraged by his side's resilience, seeing them to a win to move them six points clear at the top of the table.
With five games of the domestic season left to play, Os Verde e Brancos require 10 points to lift the 19th Primeira Liga trophy in the club's history, and their first since 2002.
Os Leoes have managed to stay at the top of the division all season by maintaining an eye-catching unbeaten record, having not lost in any of their 29 Primeira Liga games this campaign.
That has largely been down to their solid defensive record, with no side in the top flight conceding as few as the 15 goals that Amorim's men have shipped in those 29 games.
Now with just 10 points required, the Lisbon outfit will look to go one step closer to the title with a win on Saturday.
That will definitely not be easy though, as they welcome a Nacional side who will be boosted by a crucial victory last time out, putting an end to a 10-game losing run.
The basement side hosted sixth-placed Vitoria de Guimaraes on Monday, and picked up a 1-0 victory thanks to an early Pedro Mendes goal.
That put an end to a poor run for Os Alvinegros, which saw them fall to the foot of the division, having previously sat comfortably in mid-table.
Manuel Machado's side now sit six points adrift of automatic safety with five games left to play, meaning that they still have an outside chance of avoiding the drop if they can build on that positive result last time out.
However, they face one of the toughest tests that the Portuguese top flight has to offer this season, as they travel to take on the league leaders, who are yet to suffer a league defeat this campaign.
Sporting Lisbon centre-back Goncalo Inacio will be suspended for this game following his red card in the victory over Braga.
Thankfully for Amorim, they did welcome Zouhair Feddal back from injury last time out, easing their selection concerns at the back.
Paulinho is expected to lead the line, despite his slow start in the capital following his move from Braga in the January transfer window.
As a result, a lot of the responsibility has been given to Pedro Goncalves, who has thrived this season with 17 goals and four assists in 27 Primeira Liga appearances.
Matheus Nunes will be pushing for a starting spot, following his winning goal off the bench in the Braga game.
Nacional will be boosted by the return of midfielder Nuno Borges, who missed the Vitoria game through suspension.
Pedro Mendes will lead the line with renewed confidence, having netted his first goal since February to seal the 1-0 win last time out.
Sporting Lisbon possible starting lineup:
Adan; Reis, Coates, Feddal; Porro, Mario, Palhinha, Mendes; Goncalves, Paulinho, Nunes
Nacional possible starting lineup:
Filipe; Freitas, Henrique, Cesar, Correia; Camacho, Azouni, Alhassan, Borges, Gorre; Mendes
We say: Sporting Lisbon 1-0 Nacional
While the visitors will definitely come in with renewed confidence following their crucial win last time out, we do not think they have enough to topple the league leaders on Saturday.
Sporting Lisbon have the title in their sights, and that should provide enough incentive to get them over the line at the Estadio Jose Alvalade.