The visitors make the trip to Spain on the back of five matches without success, leaving them adrift at the bottom of the group.
Villarreal's unbeaten streak in all competitions has now reached 14 matches, a record which has helped the Spanish side reach the knockout stages with minimal fuss.
Nevertheless, four draws from their last five outings means that Unai Emery still has plenty to prove during his first campaign at Estadio de la Ceramica.
Although the Yellow Submarine are in third spot in the La Liga standings, a home goalless draw to Elche was not well received by the club's supporters.
Just four goals have come from their most recent five fixtures, and Emery will view this contest as an opportunity for his players to regain some confidence in the final third.
While the Spaniard will almost certainly name a weakened XI, he will want to see his squad members create extra competition for places over the Christmas period.
Qarabag would usually relish the chance to test themselves against superior opposition, but it has been a campaign to forget for Gurban Gurbanov's side.
At a time when they have been less than convincing on the domestic front, four successive defeats in Europe meant the Azerbaijani champions have long been out of contention.
On the plus side, Qarabag did manage to earn a share of the spoils at home to Maccabi Tel Aviv last week, a sign that the squad are still prepared to play for pride.
In five matches against Spanish teams, Qarabag have recorded two draws and netted two goals, the most recent defeat coming in the reverse fixture as they shipped three late strikes to lose out by a 3-1 scoreline.
Villarreal Europa League form: WWWDW
Villarreal form (all competitions): WDDDWD
Qarabag FK Europa League form: LLLLD
Qarabag FK form (all competitions): LWWLDD
Despite being substituted at half time on Sunday, Samuel Chukwueze will likely be given an opportunity in the Villarreal XI.
Paco Alcacer could return to the side after making his return from injury, potentially leading to Emery starting with two players in attack.
With Qarabag having not played at the weekend, Gurbanov may consider naming the same team which performed well against Maccabi last week.
Villarreal possible starting lineup:
Rulli; Pena, Foyth, Funes Mori, Costa; Kubo, Iborra, Coquelin, Chukwueze; Nino, Alcacer
Qarabag FK possible starting lineup:
Mahammadaliyev; Guerrier, Qarayev, Renteria, Jafarguliyev; Matic, Ibrahimli; Bayramov, Mammadov, Zoubir; Kwabena
We say: Villarreal 2-0 Qarabag FK
Even if Emery opts to rest more first-team players than usual, it is difficult to predict anything other than a comfortable home win. With Qarabag also potentially giving players the night off, they are unlikely to put up too much of a fight at Estadio de la Ceramica.