The visitors lost two of their three group-stage matches on the road last season, while the hosts are looking for their first win in major European competition since November 2005.
Brondby are taking part in their first European competition since 2008-09 when they featured in the first round of the UEFA Cup, losing 5-3 on aggregate to Rosenborg.
The Danish champions were unable to qualify for the Champions League after suffering a 4-2 aggregate defeat to RB Salzburg last month, and have now subsequently dropped down into the Europa League group stage.
Niels Frederiksen's men have made a poor start to the new campaign, winning just one of their first eight league matches this season. The Boys from Vestegnen languish in eighth place and are already 12 points behind league leaders Copenhagen.
Brondby head into Thursday's game against Sparta Prague having last faced a Czech opponent back in 2003-04, when they won 2-0 on aggregate against Viktoria Zizkov in the first round of the UEFA Cup.
Meanwhile, Sparta Prague have faced five different Danish opponents in their European history, most recently winning 3-2 on aggregate against Sonderjysk Elitesport in the 2016-17 Europa League qualifiers.
Like Brondby, the Iron Sparta failed to win their Champions League qualification tie, losing 5-1 on aggregate against Ligue 1 side Monaco, and will now participate in the Europa League group stage for the second successive year.
Sparta Prague have made a strong start to their domestic campaign, though their six-game unbeaten league run came to an end last weekend when they were beaten 3-2 against rivals Viktoria Plzen, who have now climbed above them to the summit of the Czech First League.
Pavel Vrba, who took charge of the club in February, is now hoping his side can bounce back with a victory in their opening Group A game against a Brondby outfit who will likely be considered the weakest team in the group.
Brondby centre-back Rasmus Wikstrom is set for a lengthy spell on the sidelines as he is suffering with a shoulder injury.
Paraguayan left-back Blas Riveros, who has been ruled out since November 2020 with a ruptured knee ligament injury, has an outside chance of making his return to the first team, though the 23-year-old is not expected to start if he is deemed fit to play.
As for Sparta, last season's top goalscorer Lukas Julis – who found the net 17 times across all competitions in the 2020-21 campaign – is doubtful with a groin problem.
Brondby possible starting lineup:
Hermansen; Borkeeiet, Maxso, Tshiembe; Bruus, Slimane, Radosevic, Frendrup, Mensah; Hedlund, Uhre
Sparta Prague possible starting lineup:
Nita; Wiesner, Panak, Stetina, Hancko; Sacek, Pavelka, Soucek; Moberg-Karlsson, Hlozek, Pesek
We say: Brondby 1-2 Sparta Prague
Both Brondby and Sparta Prague will view this fixture as their best chance of claiming all three points, as they aim to kickstart their Europa League campaign in positive fashion.
A closely-fought contest is set to be played out at the Brondby Stadion, though we feel that the visitors will do enough to claim a slender victory in Denmark.
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