The Bundesliga side came from behind to win 3-1 in the reverse fixture two weeks ago on their first ever trip to Serbia.
Match preview
That victory in Serbia was the last time Freiburg tasted success though, as they have slightly underwhelmed domestically since.
Christian Streich's side did put up a good fight against high-flying Bayer Leverkusen, only going down 2-1, but they were slightly fortunate to earn a point against Borussia Monchengladbach at the weekend.
Vincenzo Grifo's 96th-minute penalty saw Freiburg clinch a draw in the dying stages after being 3-1 down at half-time, helping them to avoid a third-straight defeat.
That is because they were stunned by second-tier Paderborn in the DFB-Pokal last midweek, crashing out after losing 3-1 on home soil.
Freiburg enter this clash once again as huge favourites, but they need to hope for a favour from Olympiacos in the group's other encounter, as they must better West Ham United's result to finish matchday four top of the section.
Last season's run to the Europa League last 16 was the first time Freiburg have made it past the group phase in a UEFA competition, beating Olympiacos to top spot.
In another hotly-contested group which contains the Greek giants once more, as well as Europa Conference League holders West Ham, the fight for the one automatic last 16 spot as group winners will be a close one.
The inexperience and weakness of TSC suggests that the top three are already decided, meaning regardless of group position, Freiburg will play some form of continental football in the new year.
Freiburg cannot underestimate the Serbs though, as they have taken the lead in two of their three group games so far, including the reverse two weeks ago.
In just a second-ever European campaign in their 110-year history, Backa Topola will still be dreaming of keeping the adventure going into the new year.
They were denied a group stage berth in 2020-21 when losing on penalties in qualifying to FCSB after an extraordinary 6-6 draw in a one-legged tie.
After being thumped 7-1 on aggregate by Braga in the Champions League playoffs, Zarko Lazetic's side were able to fall back on the fact they dropped straight into the Europa League group stage this season.
They have struggled in this section, as they fell to defeat to both West Ham and Freiburg despite initially going in front.
The only game where they have taken anything was the only match where they conceded first, before coming back to draw 2-2 with 10-man Olympiacos, with Milos Pantovic netting a stoppage-time equaliser.
TSC should come into this fixture on a high as well, after ending a nine-game winless run by beating fellow European contestants Cukaricki at the weekend.
Lazetic had seen some signs of improvement when they briefly threatened to end Red Star Belgrade's 119-match unbeaten home run in the league, before drawing 1-1.
Just days later, in a woeful spectacle, TSC claimed a long-awaited win though, getting the better of Cukaricki despite there only being nine shots in the entire match.
That win keeps them third in the Serbian Super Liga, a long way adrift of the top two, but seven points clear of Vojvodina in fourth, so European football looks likely against next season.
Freiburg Europa League form:
W
L
W
Freiburg form (all competitions):
L
W
W
L
L
D
Backa Topola Europa League form:
L
D
L
Backa Topola form (all competitions):
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Team News
Streich may be tempted to rotate his Freiburg side slightly here with a clash against RB Leipzig upcoming in the Bundesliga.
Roland Sallai is the most notable absentee for the hosts, and the Hungarian attacker will miss his nation's vital Euro 2024 qualifiers this month with a hip injury.
The hero from Piraeus on matchday one, Maximilian Philipp, is also out with a shoulder problem, while Daniel-Kofi Kyereh is edging nearer to a comeback after tearing his ACL.
Captain Christian Gunter remains sidelined after breaking his arm shortly after the start of the season, but he could also make a return this month.
TSC goalkeeper Veljko Ilic returned from a minor absence to start in their weekend win over Cukaricki.
Ilic was one of six players to come into the side following their draw with Red Star just days earlier, with right-back Milos Cvetkovic also returning, and he scored the clinching second goal.
Ifet Djakovac should also keep his place in midfield given his goal threat, as his equaliser against Red Star was his fifth of the season already, halfway to matching last season's tally which saw him enter double figures.
Freiburg possible starting lineup:
Atubolu; Ginter, Lienhart, Gulde; Doan, Eggestein, Hofler, Weisshaupt; Rohl, Holer, Gregoritsch
Backa Topola possible starting lineup:
Ilic; Cvetkovic, Stojic, Djordjevic, Calusic, Petrovic; Radin, Djakovac, Vulic, Cirkovic; Milovanovic
We say: Freiburg 3-0 Backa Topola
Streich should not need to go with a full-strength side to pick up three points here, but if matchday three's hat-trick hero Grifo starts, then another healthy scoreline could be in the offing.