The Bundesliga outfit ran out 2-1 victors when the two teams met at the Red Bull Arena on October 23.
While RB Leipzig find themselves in third position in the Bundesliga table, netting 14 goals in their last two outings means that Julian Nagelsmann's side are full of confidence ahead of this fixture.
Five goals were netted in each of the second half of their cup tie with Wolfsburg and the opening period of Saturday's league match with Mainz 05 - a return which will concern their hosts on Tuesday evening.
RB Leipzig have found it more difficult to find the back of the net on the European stage, but there is every suggestion that they have turned a corner in the final third.
Timo Werner is the obvious threat for the German side, with five goals coming from his last two appearances, although eight different players have gotten on the scoresheet over the past week.
As for Zenit, they head into this contest having being held to a 1-1 draw at home to CSKA Moscow on Saturday - a result which has left the club three points clear at the top of Russia's top flight.
Sergei Semak would have been disappointed to see his side fall short against one of their direct rivals, especially with their opponents playing the majority of the second half with 10 men.
Nevertheless, Zenit have enjoyed a solid start to the season, and Semak will be content with sitting in second place in this group with two home games still to come.
However, given that just three points separate the top and bottom teams, Zenit will be aware that failing to take maximum points could leave them outside of the qualification spots with two matches remaining.
Zenit St Petersburg form: WWLWWD
RB Leipzig form: DDWLWW
Aleksey Sutormin could also come into the team if Semak opts for a player with better defensive qualities down one of the flanks.
RB Leipzig were able to take their foot off the gas during the second half against Mainz at the weekend, which may encourage Nagelsmann to name the same starting lineup.
Chelsea's Ethan Ampadu finally made his Bundesliga debut off the bench, but the loanee is only likely to be among the replacements on Tuesday.
Zenit St Petersburg possible starting lineup: Kerzhakov; Santos, Ivanovic, Rakitskiy, Zhirkov; Ozdoev, Barrios, Karavaev; Azmoun, Dzyuba, Driussi
RB Leipzig possible starting lineup: Gulacsi; Mukiele, Klostermann, Upamecano, Halstenberg; Sabitzer, Laimer, Demme, Nkunku; Poulsen, Werner
We say: Zenit St Petersburg 1-2 RB Leipzig
While Zenit will begin this match as the marginal favourites, we feel that RB Leipzig have the greater momentum. With that in mind, the visitors could throw caution to the wind in order to seize full control of the group.