St Pauli beat bitter rivals Hamburg 3-0 in the 2. Bundesliga on Saturday, while Freiburg suffered a demoralising defeat away to the champions.
Match preview
Despite that 5-0 loss at the Allianz Arena to Bayern Munich, Freiburg have started the season brilliantly, and that result on Sunday was the first time they have lost a match in any competition since the second match of the season against Borussia Dortmund.
Bayern did leapfrog them in the table with that win but they still remain third in the Bundesliga, with their 11-game unbeaten run domestically and in Europe helping to propel them up the table on two fronts.
However, they have won just one of their last five league games now as a flurry of draws have halted their momentum somewhat, and they have fallen slightly off the pace of leaders Union Berlin.
Their best form has been reserved for the Europa League, as they have already qualified with a 100% record in the group and have enjoyed two fantastic away trips to Piraeus to face Olympiacos and to Nantes, winning 3-0 and 4-0 respectively.
In the domestic cup, they have suffered a string of exits at this stage in recent years but made it all the way to the final last season, before eventually losing to 10-man RB Leipzig on penalties even though they had a man advantage for over an hour.
They battled past Kaiserslautern in the first round, needing a 111th-minute winner from Ritsu Doan to see off the 2. Bundesliga side, and St Pauli may offer a similar test here.
Spirits could not be higher at St Pauli following the weekend's action, as Timo Schultz's side saw off their closest rivals Hamburg, a result which saw Hamburg surrender top spot in the 2. Bundesliga.
Not only that, it also ended a seven-game winless streak for St Pauli and moved them four points clear of the relegation zone.
They have struggled away from the Millerntor-Stadion this season though, as they have picked up just two points from six away matches, with this being a major factor in why they are so far down the table, and travelling away to the third-best team in Germany at the moment will be no stroll.
They also progressed past the first round by the skin of their teeth back in August, needing a 90th-minute winner by Jakov Medic to see off fourth division side Straelen 4-3.
However, they were very impressive in the DFB-Pokal last season, reaching the quarter-finals before losing to current Bundesliga leaders Union Berlin.
A repeat of the last competitive fixture between the two sides at this ground will go down a treat with the neutrals, as Freiburg won 4-3 in a 2. Bundesliga clash back in 2016.
Freiburg DFB-Pokal form:
W
Freiburg form (all competitions):
D
W
W
D
W
L
St Pauli DFB-Pokal form:
W
St Pauli form (all competitions):
D
D
L
D
L
W
Team News
Christian Streich has a number of lingering injury concerns going into this match, but the most recent of those is that suffered by Daniel-Kofi Kyereh, who has missed the last two matches with a muscle problem.
The Ghanaian was finding form, having scored in three successive matches before his injury ruled him out of the Europa League tie with Nantes, and he remains out.
Hungarian international Roland Sallai will also remain sidelined after fracturing his eye socket against Bayer Leverkusen back at the start of September, but the majority of Freiburg's injury worries come in defence.
Manuel Gulde, Jonathan Schmid and Kimberly Ezekwem are all absent at the back, which greatly reduces the rotation options available to Streich.
Lukas Kubler may come into the side at right-back as all his appearances this season have come in the cups so far, and he started in the first round before going off injured early on.
Schulz did not make many changes to the St Pauli side when they faced Straelen in the first round, so he should go with as strong a side as possible here and avoid any heavy rotation despite it being a cup fixture.
After the 3-0 win at the weekend, it would be a surprise to see any changes to the side that were not precautionary or for resting.
David Nemeth will be unavailable until November in defence after the Austrian was substituted with a groin problem in the first 10 minutes against Eintracht Braunschweig two weeks ago, so Adam Dzwigala should retain his place in the St Pauli back three.
Manolis Saliakas will be banned after he was sent off against Straelen, with suspensions only applying to the specific competition they happened in, so Luca-Milan Zander may be set for a first start of the season at right wing-back.
Franz Roggow and Christopher Avevor are the only other injury absentees for St Pauli going into this one, as the latter continues his recovery from a broken ankle.
Freiburg possible starting lineup:
Flekken; Kubler, Ginter, Lienhart, Gunter; Eggestein, Hofler, Jeong; Doan, Grifo, Gregoritsch
St Pauli possible starting lineup:
Vasilj; Zander, Dzwigala, Smith, Medic, Paqarada; Irvine, Afeez, Hartel; Matanovic, Amenyido
We say: Freiburg 3-0 St Pauli
Despite their excellent win at the weekend, St Pauli do not travel well and may find it very tough away to a Bundesliga side fighting near the top at the moment.