Luciano Spalletti's men failed to win either of their two previous Group G games at the Petrovsky Stadium but they need three points to boost their qualification hopes
The Group G encounter in Russia gives the hosts the chance to qualify with a win, as long as Porto fail to take all three points at home to Austria Vienna.
It will be a tough task for Luciano Spalletti's side, with visitors Atletico just one of two sides in the competition, along with holders Bayern Munich, to boast a perfect record in the group stages so far with four wins from four, including a 3-1 victory over their Russian rivals in Spain on matchday one.
Zenit boast a strong home record in Europe, having not lost in six Champions League matches, but are yet to win at the Petrovsky Stadium so far this campaign in the group stages of the competition following draws with Vienna and Porto.
Zenit also have a good record at home to Spanish opposition, with just one defeat from seven meetings with Liga outfits.
Atletico, however, have won their last two European away ties and have lost just once on their travels in all competitions this season - although they are set to rest a number of key players for the trip.
Diego Godin, Diego Costa, David Villa, Filipe Luis, Tiago, Arda Turan and Cristian Rodriguez have all been left at home for the trip to Russia, while Simeone has called up three youth players - Lucas, Ndoye and Alex Diaz - to the matchday squad.
Both sides are faring well in their domestic leagues, Zenit currently top of the Premier League, but Spalletti's men have been in poor form recently, with no win in three in the league and none in five in all competitions - their worst run since May 2006.
Atletico, meanwhile, are three points behind leaders Barcelona at the top of La Liga and are unbeaten in seven matches in all competitions. Confidence will be high in the Atletico squad approaching Tuesday's after Saturday's thumping 7-0 home win over Getafe.
Zenit will have Vyacheslav Malafeev available for the first time this season after a calf injury, while for Atletico, Adrian Lopez and Leo Baptistao (both ankle) remain doubtful for the trip to Russia.