Lazio need a win to stay top of their Europa League group and adopt a new 4-3-1-2 system against Panathinaikos with Mauro Zarate getting a chance.
The Biancocelesti were held to a 1-1 draw in Greece last time out despite dominating the match, as they didn’t do enough to secure all three points.
Coach Vladimir Petkovic admitted it was going to be tough to pick his line-up after the 4-0 defeat to Catania and just days before the Rome Derby on Sunday afternoon.
Federico Marchetti and Stefan Radu return from long-term injury lay-offs, but Hernanes, Miroslav Klose and Stefano Mauri are rested.
In this new approach, Zarate acts as trequartista behind centre-forwards Sergio Floccari and Libor Kozak, while midfielder Lorik Cana is reworked as a centre-back.
Panathinaikos are without Andre Pinto, Marinos and Ibrahim Sissoko, while Christodopoulos was fit to start despite an ankle problem.
Lazio: Marchetti; Scaloni, Cana, Ciani, Radu; Gonzalez, Ledesma, Onazi; Zarate; Floccari, Kozak
Lazio bench: Bizzarri, Biava, Candreva, Lulic, Hernanes, Mauri, Klose
Panathinaikos: Karnezis; Seitaridis, Chouchoumis, Vyntra, Spyropoulos; Zeca, Vitolo, Christodoulopoulos; Velazquez, Toché, Owusu-Abeyie
Panathinaikos bench: Kapino, Lagos, Fourlanos, Triantafyllopoulos, Barbarouses, Petropoulos, Mavrias