The Biancocelesti, on five points, have ceded top spot in Group F to Borussia Dortmund. Zenit are rock bottom with only one point and need to win to keep their hopes of qualifying alive.
Lazio didn't need any last minute heroics against Crotone as they resumed their Serie A campaign after the international break. Ciro Immobile and Joaquin Correa found the net for the Romans as Lazio ran out comfortable 2-0 winners in the pouring rain in Calabria.
Following their impressive 3-1 win over Krasnodar before the international break, Zenit Saint Petersburg kept their title challenge alive with an important 2-2 draw away to Akhmat Grozny.
Daler Kuzyaev and Dejan Lovren found the net for the defending champions, with Yaroslav Rakitskiy sent off in the final minute.
Lazio vs Zenit Saint Petersburg Head-to-Head
Matchday three was the first time Lazio and Zenit had ever played each other, with Felipe Caicedo's late goal cancelling out Aleksandr Yerokhin's first-half opener, resulting in a 1-1 draw at the Saint-Petersburg Stadium.
Zenit's last trip to Italy came in the 2014-15 UEFA Europa League campaign, where they lost their round of 16 second leg tie 1-0 to Torino, although they won 2-1 on aggregate.
Lazio form guide: D-W-D-D-W
Zenit Saint Petersburg form guide: L-W-D-W-D
Lazio vs Zenit Saint Petersburg Team News
Lazio's troubles with the coronavirus continued as Sergej Milinkovic-Savic and Luiz Felipe tested positive ahead of the trip to Crotone. Simone Inzaghi was able to name Ciro Immobile and Luis Alberto in his squad, despite the latter criticising the club on social media for their purchase of a private plane.
The treatment room continues to host Thomas Strakosha and Senad Lulic, so Pepe Reina is expected to continue in goal. Inzaghi is likely to rotate his XI as he embarks on a run of 10 games in 33 days.
Injuries: Thomas Strakosha, Senad Lulic, Gonzalo Escalante
Covid-19: Sergej Milinkovic-Savic, Luiz Felipe
Zenit Saint Petersburg
Sergey Semak lost right back Vyacheslav Karavaev to injury in the game against Akhmat. Danil Krugovoy may be drafted in as an emergency option. Yaroslav Rakitskiy is suspended for the next league game, so he is certain to start alongside Dejan Lovren.
Sardar Azmoun, Magomed Ozdoev and Sebastian Driussi are doubts for this game, with midfielder Wendel out with a muscle injury.
Injuries: Wendel, Vyacheslav Karavaev
Doubtful: Sardar Azmoun, Magomed Ozdoev, Sebastian Driussi
Lazio vs Zenit Saint Petersburg Predicted Lineups
Lazio Predicted XI (3-5-2): Pepe Reina (GK); Patric, Wesley Hoedt, Stefan Radu; Marco Parolo, Andreas Pereira, Danilo Cataldi, Jean-Daniel Akpa Akpro, Adam Marusic; Felipe Caicedo, Ciro Immobile
Zenit St Petersburg Predicted XI (4-1-4-1): Mikhail Kerzhakov (GK), Danil Krugovoy, Dejan Lovren, Yaroslav Rakitsky, Douglas Santos; W.Barrios; Aleksandr Yerokhin, Daler Kuzyaev, Andrey Mostovoy, Yuri Zhirkov; Artem Dzyuba
Lazio vs Zenit Saint Petersburg Prediction
Zenit caused Lazio plenty of problems in the reverse fixture in Russia, but with mounting injuries, the visitors are unlikely to trouble their Italian hosts this time.
Lazio are unbeaten in seven games, and with Ciro Immobile back, they should be favorites to earn all three points at the Stadio Olimpico.
Prediction: Lazio 2-1 Zenit Saint Petersburg