Ivan Provedel is able to start for Lazio, but Maurizio Sarri transforms his attack with Gustav Isaksen and Taty Castellanos against rock bottom Celtic.
It kicks off at the Stadio Olimpico at 17.45 GMT.
This is a huge opportunity for the Biancocelesti, because Celtic are in last place with just one point, while Atletico Madrid and Feyenoord face off in the other game.
Atleti are top with 8 points, Lazio 7 and Feyenoord 6, so it is wide open for qualification to the Round of 16.
Goalkeeper Provedel was a major doubt with flu symptoms including a fever, but he has recovered in time to start.
Coach Maurizio Sarri has many more problems after Saturday’s shock Serie A defeat to Salernitana, as Matias Vecino is suspended, with Alessio Romagnoli, Mattia Zaccagni and Nicolò Casale all injured.
The big surprises are upfront, choosing Isaksen, Castellanos and Felipe Anderson for the trident, sending Ciro Immobile and Pedro to the bench.
Celtic have issues too, as both Daizen Maeda and Luis Palma sit out bans, with Reo Hatate and Liel Abada carrying muscular injuries.
Former Torino goalkeeper Joe Hart is between the sticks, but Kyogo Furuhashi and James Forrest are the ones to watch upfront, with 21-year-old South Korean winger Hyun-jun Yang.
Their only point came in a 2-2 draw with Atletico Madrid, but Celtic were then thumped 6-0 in Spain when down to 10 men.
Lazio: Provedel; Lazzari, Gila, Patric, Marusic; Guendouzi, Rovella, Luis Alberto; Isaksen, Castellanos, Felipe Anderson
Lazio bench: Sepe, Magro, Pellegrini, Kamada, Pedro, Immobile, Hysaj, Cataldi, Ruggeri
Celtic: Hart; A Johnston, Carter-Vickers, Scales, Taylor; O’Riley, McGregor, Paulo Bernardo; Hyun-jun Yang, Furuhashi, Forrest
Celtic bench: Bain, Morrison, Lagerbielke, Phillips, Turnbull, Holm, Oh, Ralston, Welsh, Frame, M Johnston
Ref: Meler (TUR)
Player statistic
27' | Greg Taylor | |||
35' | Alistair Johnston |
Nicolò Rovella | 51' | |||
71' | Matt O’Riley | |||
78' | Hyun-jun Yang | |||
Ciro Immobile | 82' | |||
Ciro Immobile (Assist: Gustav Isaksen) |
85' | |||
Pedro | 89' | |||
Patric | 90+3' |