Die Roten Bullen are fourth in the Bundesliga with 21 points but were beaten 5-1 by Wolfsburg on November 30, while the away side are second with 26 points and defeated Heidenheim 4-0 on Sunday.
Match preview
RB Leipzig conceded three goals in the first 16 minutes against Wolfsburg and scored their only goal of the game in the 82nd minute when they were trailing 4-0.
Rose has come under significant pressure for results of late, with the club having lost five and drawn one of their past six games.
Die Roten Bullen boss spoke about his position as head coach in the aftermath of his side's defeat against Wolfsburg, saying: "I was the right coach when we didn't lose in 19 games but I also know that questions arise."
Leipzig beat St Pauli 4-2 on October 29 in the previous round of the DFB-Pokal and have been excellent in the competition in recent years, winning the competition in 2021-22 and 2022-23, while finishing as runners-up in 2018-19 and 2020-21.
The hosts have lost three, drawn one and triumphed in two of their last six home matches, and have won their seven most recent DFB-Pokal outings at Red Bull Arena.
As for Eintracht Frankfurt, their 4-0 win against Heidenheim was spearheaded by Omar Marmoush, who scored twice and helped close the gap to Bundesliga leaders Bayern Munich to just four points.
The Eagles beat Borussia Monchengladbach 2-1 on October 30 in their prior outing in the DFB-Pokal, a game in which they had a player sent off in the 15th minute but still managed to achieve victory.
Head coach Dino Toppmoller's side have scored 31 times and conceded on 16 occasions in the top flight, and these records make them the league's second best offensive and joint fifth best defensive club.
Toppmoller's team are in outstanding form considering they have achieved victory in each of their last seven games, and are unbeaten in their past eight in all competitions.
Eintracht Frankfurt have also been strong on the road this term having won six of their eight most recent away fixtures.
RB Leipzig DFB-Pokal form:
W
W
RB Leipzig form (all competitions):
L
L
D
L
L
L
Eintracht Frankfurt DFB-Pokal form:
W
W
Eintracht Frankfurt form (all competitions):
W
W
W
W
W
W
Team News
Leipzig have numerous injury absentees and will not be able to call upon defenders Castello Lukeba, David Raum, El Chadaille Bitshiabu and Lukas Klostermann, so expect to Rose to select a back four of Lutsharel Geertruida, Willi Orban, Nicolas Seiwald and Benjamin Henrichs.
Midfielders Eljif Elmas and Forzan Assan Ouedraogo are also ruled out, and in their absence Arthur Vermeeren and Kevin Kampl may start in a double pivot.
Xavi Simons and Yussuf Poulsen will be unavailable due to injury, so strikers Benjamin Sesko and Lois Openda could be supported by Christoph Baumgartner and Antonio Nusa.
Opponents Eintracht Frankfurt have a comparatively healthy squad considering centre-back Aurele Amenda is their only injury concern.
Tuta and Robin Koch are likely to be chosen in the heart of defence, while Ellyes Skhiri and Hugo Larsson could partner each other in midfield.
RB Leipzig possible starting lineup:
Gulacsi; Geertruida, Orban, Seiwald, Henrichs; Baumgartner, Vermeeren, Kampl, Nusa; Sesko, Openda
Eintracht Frankfurt possible starting lineup:
Trapp; Collins, Tuta, Koch, Theate; Knauff, Skhiri, Larsson, Gotze; Ekitike, Marmoush
We say: RB Leipzig 1-3 Eintracht Frankfurt
Die Roten Bullen are in the midst of an injury crisis, and it is difficult to see how they can showcase their best level on Wednesday.