Lazio look set to use Milan Badelj and Luis Alberto in the absence of Lucas Leiva, while Milan lean towards Fabio Borini and an all-new defence.
It kicks off at the Stadio Olimpico at 17.00 GMT, click here for a match preview.
The game will be available in the UK and Ireland on Eleven Sports on mobile, online and via connected TV sets. Click here to watch now!
This is a head-to-head for Champions League ambitions and a top four finish, as only one point separates them going in.
Lazio are without Lucas Leiva, so Badelj is expected to get the midfield nod rather than Danilo Cataldi.
Luis Alberto is the favourite to support Ciro Immobile, although there is strong competition from Felipe Caicedo and Joaquin Correa.
Milan’s injury crisis drags on with long-term issues for Alessio Romagnoli, Giacomo Bonaventura, Lucas Biglia, Mateo Musacchio, Mattia Caldara and Ivan Strinic.
Gonzalo Higuain begins his two-match ban after the meltdown against Juventus, so Patrick Cutrone has to lead the way.
It’s inevitably a new defence with Ignazio Abate, Cristian Zapata and Ricardo Rodriguez trying to form a three-man unit, while there are still doubts over the wing-backs.
Davide Calabria and Hakan Calhanoglu have shaken off knocks and should start, but Fabio Borini is now the favourite to start rather than Diego Laxalt.
Franck Kessie has to be careful, as he is one yellow card away from a ban and Milan have Parma next week.
Lazio (3-5-1-1): Strakosha; Wallace, Acerbi, Radu; Marusic, Parolo, Badelj, Milinkovic-Savic, Lulic; Luis Alberto; Immobile
Lazio bench: Proto, Guerrieri, Bastos, Caceres, Luiz Felipe, Patric, Lukaku, Cataldi, Murgia, Berisha, Correa, Caicedo
Milan (3-5-2): G Donnarumma; Abate, Zapata, Rodriguez; Calabria, Kessie, Bakayoko, Borini; Suso, Calhanoglu; Cutrone
Milan bench: Reina, Plizzari, Conti, Simic, Bertolacci, Mauri, Montolivo, Laxalt, Castillejo, Halilovic, Tsadjout