Dortmund, meanwhile, will be determined to bounce back from their 4-2 thrashing at the hands of Bayern Munich at the weekend.
Leipzig suffered a hugely disappointing defeat in the Bundesliga themselves last time out, with Marco Rose’s side losing 3-0 at home to Mainz 05.
With Champions League qualification rivals Freiburg held to a 1-1 draw at home to Hertha Berlin, victory for Die Roten Bullen would have been enough to move themselves above Christian Streich’s side into fourth spot.
However, Marcus Ingvartsen’s ninth-minute strike put them on the back foot for the rest of the encounter, with Bo Svensson’s side always proficient in transition. Despite Leipzig dominating possession with 70% of the ball, Mainz registered more shots and corners than the hosts and deserved their victory.
Four defeats in their last five matches in all competitions comfortably represents Rose’s poorest spell since taking charge last September, so the 46-year-old will be highly motivated to get one over on his former club in midweek.
Having never won a major honour as a manager in German football, Rose will recognise that retaining this competition provides Leipzig’s best opportunity of marking this campaign as a successful one, even if they do end up qualifying for Europe’s elite competition too.
Dortmund, meanwhile, saw their hopes of ending a 10-year wait for the Bundesliga title severely damaged by a 4-2 defeat to the reigning champions at Allianz Arena on Saturday.
The latest rendition of Der Klassiker’s scoreline hugely flattered BVB, too, with Edin Terzic’s side scoring two late consolation goals after Kingsley Coman’s close-range effort had made it 4-0 to the Bavarians inside a ruthless opening 50 minutes.
Gregor Kobel’s disastrous own goal set the tone for the rest of the title clash, with the Switzerland goalkeeper miskicking Dayot Upamecano’s attempted through ball and diverting the ball into his own net, before Thomas Muller’s quickfire brace ended the match as a contest.
Dortmund remain firmly in the title race, of course, considering that they only trail Bayern by two points at the summit, but they must navigate their way through a tricky fixture against fellow challengers Union Berlin this weekend if they are to realistically stay in the hunt.
In the meantime, Terzic will be keen for his players to leave all avenues of winning a trophy wide open, especially having already tasted success in this competition two seasons ago. Having beaten Leipzig only a month ago, he will be confident of making it to the last four.
RB Leipzig DFB-Pokal form:
RB Leipzig form (all competitions):
Borussia Dortmund DFB-Pokal form:
Borussia Dortmund form (all competitions):
We say: RB Leipzig 2-1 Borussia Dortmund
This has all the makings of an excellent cup tie, with both teams recognising that the DFB-Pokal represents their best chance of winning silverware this season.
Dortmund could be bruised by their defeat to Bayern on Saturday, with home advantage potentially set to be a key factor in helping Leipzig remain in the hunt to retain this trophy.