Last season's top two are set to go head-to-head for the first time this season in the biggest tie of the round, which sees Die Roten Bullen already in a better position than in last season's competition, which saw them knocked out in the first round.
The tie should also prove an indicator of what lies in store when the two meet in the Bundesliga in just three days.
Leipzig in rich vein of form despite congested schedule
Leipzig's qualification for the Champions League last season means that their schedule is an awful lot more hectic this time around, with no less than three competitions on Ralph Hassenhüttl's mind.
Die Roten Bullen have not shown any signs of fatigue so far though and have won their last four games in all competitions, in addition to being unbeaten at home since the thrilling 5-4 defeat against Bayern in May.
Away wins against FC Köln and league leaders Borussia Dortmund have been complemented by wins at the Red Bull Arena against FC Porto and most recently VfB Stuttgart, with Marcel Sabitzer's first-half strike ensuring Leipzig stayed within a point of top spot.
Last season's top-scorer Timo Werner has carried on from where he left off, scoring six goals in 11 appearances so far this season while summer signing Jean-Kévin Augustin has impressed with four goals and two assists in 10 games.
Could an old face rejuvenate Bayern?
Jupp Heynckes just can't stay away from Munich - this is his fourth spell as Bayern manager, previously occupying the hotseat from 1987 to 1991, as caretaker in 2009 and from 2011 to 2013.
The 72-year-old will be hoping to repeat his Champions League, Bundesliga and DFB-Pokal treble of 2012/13 with the Bavarians by the end of the season when he is due to be succeeded by an as yet unknown boss.
For now Heynckes and Bayern must focus on the task at hand, which on Wednesday happens to be finding a way past a Leipzig side who are on top of their game, but Heynckes' men have been no slouches themselves since he took the reigns.
Bayern have won three from three with him at the helm and have not conceded since their 2-2 draw at Hertha Berlin on October 1, scoring nine goals in their last three matches against SC Freiburg, Celtic and Hamburger SV.
The Bavarians have been somewhat reliant on talisman Robert Lewandowski for goals this season, but when the Polish forward can score 13 goals in 14 games his team-mates can be forgiven for not shouldering some of the burden.
Right-back Joshua Kimmich has been in unusual form in front of goal in recent outings, netting twice in his last three games.
Leipzig's committments in both the Bundesliga and Champions League mean there is likely to be a good amount of squad rotation Wednesday, with players such as Kevin Kampl and Augustin set to return after being rested at the weekend while winger Bruma is likely to miss out via injury.
Heynckes will be without attacking pair Thomas Müller and James Rodríguez for the cup tie due to injuries, while Javi Martínez could return to the side after overcoming a shoulder problem.
RB Leipzig (4-4-2): Gulacsi; Klostermann, Orban, Upamecano, Halstenberg; Forsberg, Demme, Kampl, Sabitzer; Werner, Augustin.
Bayern Munich (4-2-3-1): Ulreich; Alaba, Hummels, Boateng, Rafinha; Martínez, Rudy; Robben, Thiago, Coman; Lewandowski.