Udinese and Lazio are both desperate to turn their form around and veterans Antonio Di Natale and Miroslav Klose go head-to-head.
It kicks off at the Stadio Friuli at 11.30 GMT, click here for a match preview.
Both Francesco Guidolin and Edy Reja urged their sides to set aside fear and embrace enthusiasm in their pre-game Press conferences this weekend.
Udinese were crushed 3-0 in an ill-tempered trip to Sampdoria last week and the two red cards see Allan and Gabriel Silva suspended for this tie.
Zeljko Brkic has shaken off a neck problem to get back in goal, while Luis Muriel is back on the bench after two months out injured.
Di Natale is supported by ‘O Mago’ Maicosuel, while Roma-owned Nico Lopez is on the bench.
Lazio have been in chaos for the last month, sacking Vladimir Petkovic for breach of contract – something the Coach is contesting with his lawyers – and bringing back his predecessor Reja.
The tactician had a fantastic debut, beating Inter, but last week’s draw away to Bologna saw his players jeered off the pitch.
Stefan Radu, Abdoulay Konko and Alvaro Gonzalez are injured, while Cristian Ledesma and Stefano Mauri are suspended.
Federico Marchetti is back in the squad, but not fit to start so Etrit Berisha is again in goal, but Reja switches to a 3-4-1-2 system with Sergio Floccari partnering Klose and Antonio Candreva in a trequartista role.
Exciting Nigerian youngster Eddy Onazi is given the midfield keys, as off-form Hernanes is dropped.
Lazio’s record at the Stadio Friuli is very poor indeed, as they haven’t conquered this arena since a thrilling 4-2 victory in 2006-07. This fixture has not ended goalless since November 1992.
Udinese: Brkic; Heurtaux, Danilo, Domizzi; Basta, Pinzi, Pereyra, Badu, Douglas; Maicosuel, Di Natale
Lazio: Berisha; Ciani, Dias, Biava; Cavanda, Biglia, Onazi, Lulic; Candreva; Klose, Floccari