The 2. Bundesliga side emerged as 4-0 victors against Bremer SV in the first round of the competition in August, while the visitors progressed to the second round after they beat Energie Cottbus 3-1 in August.
Match preview
Paderborn finished seventh in the second tier with 52 points from 34 games last term and ended the season 11 points from third-placed Fortuna Dusseldorf, who secured the league's promotion playoff spot.
This campaign, the hosts are third with 19 points from 10 games and level on points with second-placed Hannover 96 and one point from leaders Fortuna Dusseldorf, who occupy the 2. Bundesliga's automatic promotion spots.
Boss Lukas Kwasniok's side beat FC Koln 2-1 last time out in the league on October 25, a match in which his side conceded first in the 66th minute but claimed all three points after goals from Sven Michel in the 76th and 80th minutes.
Kwasniok's team have lost just once in their last 13 matches, winning eight and drawing four in that period.
The home side have also won five of their last six games at Home Deluxe Arena, though they have lost three of their last five home fixtures in the DFB-Pokal.
Opponents Werder Bremen come into the clash having drawn 2-2 against Bundesliga champions Bayer Leverkusen on Saturday in the league, with Romano Schmid scoring a 90th-minute equaliser for the Green-Whites.
Manager Ole Werner was delighted with the point, saying that his players defended brilliantly and gave up very few chances while posing a threat in the final third themselves.
Werner's side have scored 14 goals and conceded 16 times, and these records make them joint seventh-best offensive and joint fifth-worst defensive team in the top flight.
The Green-Whites have been eliminated from the DFB-Pokal by lower-league opposition three times in the last three seasons, including by Paderborn on penalties in October 2022 after the sides drew 2-2.
To their credit, Werder Bremen have won their three most recent away games, scoring on 10 occasions and conceding six goals in that time.
SC Paderborn DFB-Pokal form:
W
SC Paderborn form (all competitions):
D
W
D
W
L
W
Werder Bremen DFB-Pokal form:
W
Werder Bremen form (all competitions):
W
L
W
L
W
D
Team News
The hosts will not be able to select goalkeeper Arne Schulz until early November, while centre-back Visar Musliu will not make a comeback until February 2025 as a result of a broken ankle.
Midfielders Mattes Hansen and Sebastian Klaas are also ruled out, while forward Felix Platte is not scheduled to return until early next month.
Markus Schubert will likely start in goal for Paderborn behind centre-backs Felix Gotze and Calvin Brackelmann, while Luis Engelns and Santiago Castaneda may start in a double pivot.
Meanwhile, Werder Bremen will be without midfielder Jens Stage due to a calf injury, as well as centre-back Niklas Stark due to a hip issue.
Amos Pieper, Marco Friedl and Miloz Veljkovic may be selected in the heart of defence in front of goalkeeper Michael Zetterer.
Leonardo Bittencourt, Senne Lynen and Romano Schmid are candidates to start in a midfield three, while Keke Topp and Marvin Ducksch could start in a front two.
SC Paderborn possible starting lineup:
Schubert; Hoffmeier, Gotze, Brackelmann; Obermair, Engelns, Castaneda, Zehnter; Bilbija, Kostons, Ansah
Werder Bremen possible starting lineup:
Zetterer; Pieper, Friedl, Veljkovic; Weiser, Schmid, Lynen, Bittencourt, Agu; Topp, Ducksch
We say: SC Paderborn 2-1 Werder Bremen
Given Werder Bremen's recent history of being knocked out of the DFB-Pokal by lower-league opposition, it would not be surprising if they were eliminated by Paderborn on Wednesday.