While the Scudetto looks set to return to the Juventus Stadium at the end of the campaign, Roma and Napoli have been in impressive form nonetheless.
However, Rafael Benitez's hopes of a title in his first Napoli season will be mathematically ended, unless his side can snap the seven-match winning run in Serie A built up by Antonio Conte's charges.
Napoli continued their recent fixture schedule with a 4-2 win over Catania on Wednesday and will need all the rest and recuperation they can get ahead of the Juve clash - after the champions ran out 3-0 winners in November's reverse fixture.
Jose Callejon, who found the net in the Catania victory, has refused to give up on second place and insists Napoli will close the gap to Juve next season.
"We believe in second and we will do all we can to get it," he told Radio Kiss Kiss Napoli.
"The Champions League is an important objective for us and we want to get there automatically.
"Scudetto? Juve are very strong – but next season we'll fight with them, there's no doubt about that."
If Napoli can spring a surprise and halt the Juve title charge, Roma will be heavy favourites to close the gap at the top when they take on lowly Sassuolo though relegation-zone rivals Catania and Livorno also face tough tests in the fight for survival.
Catania travel to face face an Udinese side unbeaten in their last six home games, while Livorno host Inter, having lost the sides' last five meetings.
Livorno may draw hope from Inter's run of just two wins from their last seven outings at San Siro and Walter Mazzarri called for his side to be more "cynical" after they dropped points for the second time in a week in Thursday's 0-0 draw with Udinese.
Inter's main rivals for UEFA Europa League qualification, Fiorentina and Parma, have been somewhat inconsistent themselves - something they will look to arrest against Sampdoria and Lazio respectively.
After picking up a first win in six games against Fiorentina on Wednesday, Milan host Chievo while Bologna will look to edge further clear of the drop zone when they take on in-form Atalanta.
A 1-0 midweek win over Verona boosted Cagliari's survival hopes and they will hope for further success against Torino, while Andrea Mandorlini's side will be desperate to end a four-game losing sequence when they host Genoa.
