Cagliari had a strong start under Walter Mazzarri and are looking for the victory against an Empoli side who have lost their way.
It kicks off at the Sardegna Arena at 17.30 UK time (16.30 GMT).
The Sardinians sacked coach Leonardo Semplici and replacement Mazzarri had a good debut, drawing 2-2 away to Lazio.
Gabriele Zappa is suspended, with Marko Rog, Damir Ceter and Paolo Faragò injured, so Nahitan Nandez moves wide right.
Diego Godin and Kevin Strootman are back in the squad after injury.
Empoli lurched from victory at the Juventus Stadium to surprise defeats against Venezia and Sampdoria.
Lorenzo Tonelli, Paolo Bandinelli, Samir Ujkani and Riccardo Fiamozzi are unavailable, but Andrea Pinamonti replaces Patrick Cutrone upfront.
Cagliari: Cragno; Walukiewicz, Ceppitelli, Carboni, Lykogiannis; Nandez, Marin, Deiola, Dalbert; Joao Pedro, Keita
Empoli: Vicario; Stojanovic, Romagnoli, Viti, Marchizza; Zurkowski, Ricci, Henderson, Haas; Di Francesco, Pinamonti