Lazio and Sassuolo are both in dire need of a victory and face off in an extremely tense atmosphere.
It kicks off at 19.45 GMT, click here for a match preview.
Biancocelesti fans are staging a protest against President Claudio Lotito this evening with a march through the streets ahead of the game, so the Stadio Olimpico is going to be a fiery cauldron for the hosts.
Edy Reja replaced Vladimir Petkovic over Christmas, but suffered back-to-back defeats against Catania and Europa League opponents Ludogorets.
Confidence is low once more and fatigue a problem after Thursday’s continental commitments, while Bruno Pereirinha, Helder Postiga and Ederson are injured.
Federico Marchetti is again benched in favour of Etrit Berisha with Miroslav Klose supported by Antonio Candreva, Senad Lulic and Stefano Mauri in another system change.
Sassuolo have lost all three games under Alberto Malesani and are locked in the relegation zone.
There is a lengthy list of absentees, including Emanuele Terranova, Masucci, Thomas Manfredini, Alexe and Francesco Acerbi.
Domenico Berardi is their star player in attack, but the Under-21 international is surprisingly benched.
Instead, Simone Zaza is partnered by Sergio Floccari, who only left Lazio in January.
There have been numerous changes in recent weeks, including the arrival of Paolo Cannavaro, who had been heavily linked with a move to Lazio.
Luca Marrone and Luca Antei are also dropped.
Lazio: Berisha; Konko, Biava, Dias, Radu; Ledesma, Gonzalez; Candreva, Mauri, Lulic; Klose.
Lazio bench: Marchetti, Strakosha, Novaretti, Cavanda, Cana, Ciani, Biglia, Onazi, Keita, Kakuta, Anderson, Perea
Sassuolo: Pegolo; Mendes, Cannavaro, Ariaudo; Rosi, Chibsah, Magnanelli, Biondini, Longhi; Floccari, Zaza
Sassuolo bench: Pomini, Antei, Pucino, Bianco, Gazzola, Ziegler, Marrone, Missiroli, Farias, Floro Flores, Sansone, Berardi
Think you know your Italian football? Share your knowledge, tips and comments to win cash prizes in OLBG's tipster competition - £11,000 to be won monthly!