Lazio have Tommaso Rocchi supported by Mauro Zarate, Hernanes and Stefano Mauri against Lecce in their bid for Champions League qualification.
The Biancocelesti still have a slender hope of reaching fourth place, as they need to win at the Stadio Via del Mare and hope Udinese lose at home to Milan.
It is also true that they have to defend fifth place from Roma, who could leapfrog them to get a later start in the Europa League.
Francelino Matuzalem has joined Mark Bresciano, Stefan Radu, Mourad Meghni, Simone Del Nero and Mobido Diakite' on the treatment table.
Coach Edy Reja has opted for a 4-2-3-1 system with veteran Rocchi leading the way ahead of Mauri, Hernanes and Zarate in a wider role.
Lecce have already secured their safety and are in the mood to celebrate with Ignacio Piatti and David Di Michele up front.
There is an all-new central defensive pairing of Alberto Giuliatto and Guillermo Giacomazzi.
Nenad Tomovic is suspended along with the long list of injuries: Edward Ofere, Ruben Olivera, Stefano Bertolacci, Stefano Ferrario, Gustavo and Sini.
Lecce: Benassi; Donati, Giacomazzi, Giuliatto, Brivio; Munari, Vives, Coppola, Mesbah; Piatti, Di Michele
Lazio: Muslera; Lichtsteiner, Biava, Dias, Garrido; Ledesma, Brocchi; Mauri, Hernanes, Zarate; Rocchi
Betting on Serie A? Bet365 are offering a 100% deposit bonus, up to £200 - find out more