Qurban Qurbanov's side can secure their place in the knockout round if they match or better the result of Nantes in Group G's other encounter.
Match preview
Qarabag reached the preliminary knockout round of the UEFA Europa Conference League last season, but progression here would be the first time they have ever played European football post-Christmas at this level.
They come into the game knowing their destiny is in their own hands too, sitting one point clear in second place.
Their 3-0 thrashing of Nantes on matchday two means they have the upper hand over the French outfit on head-to-head record - the determining factor should there be a tie on points.
Therefore, as long as Nantes do not win in Piraeus against Olympiacos, Qarabag will go through, but the Greek side are bottom of the group without a win, so the Azeri's may need to do the work themselves.
They would have already sealed progression if not for a 95th-minute winner by Ignatius Ganago for Nantes which broke Qarabag hearts last week, a goal which has kept the group alive going into the final matchday.
Qarabag have played a weakened side for domestic matches recently to focus on Europe and they still have a 100% record after 11 games in the Premyer Liqasi, with their only defeats this season all coming in away games on the continent.
No side has come to Baku and beat Qarabag since Marseille in that UECL preliminary knockout round encounter back in February, 21 matches ago.
Freiburg are a long way clear in the group, safely qualified as group winners on 13 points, with a draw against Olympiacos last time out being their first dropped points of the campaign.
Qarabag's eventual defeat at Nantes last week means Freiburg were through regardless of how they got on, but Lukas Kubler still scored a 93rd-minute equaliser to eliminate the Greeks.
Christian Streich's men have responded superbly to their 5-0 drubbing at the hands of Bayern Munich just over two weeks ago, progressing in the DFB-Pokal, progressing in Europe, and recording back-to-back wins in the Bundesliga.
A 2-0 win at Schalke on Sunday kept them in third, two points off Union Berlin who remain the surprise Bundesliga leaders.
Vincenzo Grifo put on a masterclass at the Veltins Arena, and the Italy international will get a nice break during the World Cup, like a lot of the Freiburg squad, to recharge for the second half of the season.
Qarabag FK Europa League form:
L
W
W
D
L
Qarabag FK form (all competitions):
L
L
W
W
D
L
Freiburg Europa League form:
W
W
W
W
D
Freiburg form (all competitions):
W
L
W
W
D
W
Team News
Filip Ozobic was the only player who started for Qarabag in the weekend win over Shamakhi from the side which went down in Nantes last week.
Ozobic only lasted 18 minutes though before going off injured, allowing Nariman Akhundzade a chance to make his debut for the club.
Qurbanov is expected to make another 11 changes to the side for this encounter, with their squad so superior to the rest domestically, they are able to field a second string lineup in the league, saving their main squad of players for Europe.
Four of the European starters were given some minutes in the second half to help seal their 4-0 win on Sunday, but Marko Vesovic and captain Qara Qarayev were left out of the squad entirely.
Leandro Andrade and Badavi Huseynov are the injury absentees for Qarabag here.
With Freiburg already through as group winners and going strong in Germany, wholesale changes are expected from Streich for this trip, with some key players to be left at home.
They could name a similar side to the one that faced St. Pauli in the DFB-Pokal a few weeks back, with Nils Petersen given a rare start up front and Noah Atubolu given a go between the sticks.
Manuel Gulde (back), Kimberly Ezekwem (tendon), Roland Sallai (eye) and Jonathan Schmid (muscle) all remain out injured.
Qarabag FK possible starting lineup:
Mahammadaliyev; Vesovic, Mustafazada, Medina, Cafarquliyev; Qarayev, Richard Almeida, Kady; Sheydayev, Owusu, Zoubir
Freiburg possible starting lineup:
Atabolu; Sildillia, K Schlotterbeck, Lienhart, Gunter; Hofler, Kietel, Schade, Jeong, Weisshaupt; Petersen
We say: Qarabag FK 2-1 Freiburg
Freiburg, despite being by far the best team in the group, have nothing to play for and have important matters to attend to in the Bundesliga over the next week and a half, so are unlikely to take many first-team regulars to Azerbaijan.