Cagliari will hope a strong home record against Empoli and a new coach can see them claim their first win since January.
Zdenek Zeman will begin his mission to save Cagliari from relegation to Serie B against Empoli as the majority of Serie A's struggling sides face tougher tests.
Zeman, 67, was rehired as coach by Cagliari on Monday to replace Gianfranco Zola, who had only taken over from the Czech on December 24.
Cagliari have not won in six matches, losing five, but they should be confident on Saturday against 14th-placed Empoli, who have not won in Sardinia since 2002.
Zola's eight-game stint in charge of Cagliari led to two wins and four defeats, leaving the club in 18th - the highest of Serie A's three relegation slots.
But Cagliari could surge away from fellow drop-zone outfits Cesena and Parma, who face Inter and Sassuolo, respectively.
Atalanta, who sit 17th, host 12th-placed Udinese, while Chievo will travel to seventh-placed Genoa on Sunday.
Empoli, however, have their own reasons to believe in victory, as they have not lost in six games.
Leaders Juventus will play in the other match on Saturday as they visit Palermo.
Juve winger Simone Pepe, who has played in his club's past two matches in all competitions after approximately two-and-a-half years battling injuries, hopes to be involved again.
Palermo's 10-game unbeaten run at their Stadio Renzo Barbera has Pepe wary of Juventus' hosts.
"We need to keep our focus because Palermo have gone a long time without losing a home game and we must try to stretch our advantage over Roma," Pepe told Juve's website.
Juventus lead second-placed Roma by 11, with Lazio, Napoli, Fiorentina and Sampdoria completing the top six.
Roma will host Sampdoria on Monday, Lazio will visit Torino, Napoli travel to Hellas Verona and Fiorentina take on Milan.