After beating Sturm Graz last time out, the French side are anticipating their first ever away game in European competition, while their hosts suffered a major setback on the opening matchday.
Match preview
Despite dominating possession on away soil, Salzburg found themselves on the wrong end of a 3-0 scoreline in their league-phase opener, as Sparta Prague side clinically picked them off, scoring all three goals before the hour mark.
Die Roten Bullen may have had a 71% share of the ball - their highest on record in a Champions League fixture - but they still only managed to record a single shot on target.
Making their sixth successive appearance in UEFA's top club competition, Salzburg have become part of the furniture over recent years, but their current winless run of six games - of which they lost five - is the longest they have endured to date.
Indeed, they have been beaten in each of their last four home matches in the Champions League group stage, including all three last term; previously, they had gone six in a row without defeat at Red Bull Arena.
Having followed failure in Prague with a goalless draw against WSG Tirol in the Bundesliga, the side managed by ex-Liverpool coach Pep Lijnders were back on winning form last weekend, when an Oscar Gloukh goal in each half saw off the challenge of Austria Wien.
Lijnders will hope that success can instigate a more positive streak for a team occupying an unusually modest fourth place in their domestic standings, having seen their run of 10 titles ended by Sturm Graz last term.
While Salzburg had a night to forget on the opening matchday, Brest were busy beating none other than Sturm Graz on their long-awaited European debut.
For the first time in the club's 121-year history, Les Pirates entered continental competition, and the fairytale had a suitable conclusion when long-serving midfielder Hugo Magnetti scored the opener at their temporary 'home' of Stade Roudourou in Guingamp.
Brighton & Hove Albion loanee Abdallah Sima secured maximum points shortly after the break, so Brest will now try to become just the second French team ever to win their first two matches in either the European Cup or Champions League - and the first in some 45 years.
Furthermore, the last Ligue 1 team to win their first away fixture at the elite level was Auxerre back in 1996, and six sides from France have since tried and failed.
However, Eric Roy's squad - who finished third last season, with a club-record 61 points - will travel to Austria on the back of some dismal domestic form.
With two league wins and four losses on the board, following a 3-0 defeat to Auxerre on Friday evening, Brest have now conceded 14 goals and kept only two clean sheets across all competitions.
Red Bull Salzburg Champions League form:
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D
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L
Red Bull Salzburg form (all competitions):
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D
L
L
D
W
Brest Champions League form:
W
Brest form (all competitions):
L
W
L
W
W
L
Team News
Pep Lijnders will again be without influential midfielder Maurits Kjaergaard this week, due to an ankle injury that could keep the Denmark Under-21 international sidelined until November.
Serbian left-back Aleksa Terzic (hamstring) is also set to miss out, while Samson Baidoo (calf) remains a doubt; long-term absentees Daouda Guindo and Takumu Kawamura are still unavailable.
One man ready to start for Salzburg is Oscar Gloukh: since the start of last season, he is one of only three players aged under 21 to have both created 10 or more chances and completed 10 or more dribbles in the Champions League - the others are Lamine Yamal and Warren Zaire-Emery.
Liverpool loanee Stefan Bajcetic was one of five Champions League debutants in Die Roten Bullen's starting XI last time out, but Brest's squad is even less experienced at the top level.
The visitors are again missing defensive duo Bradley Locko (Achilles) and Achraf Dari (ankle), plus midfielder Pierre Lees-Melou (leg), the latter of whom has only just returned to full training.
Centre-back Julien Le Cardinal missed Friday's Ligue 1 loss through illness, so Soumaila Coulibaly - on loan from Borussia Dortmund this season - and Brendan Chardonnet could be paired in defence.
Red Bull Salzburg possible starting lineup:
Blaswich; Morgalla, Piatkowski, Blank, Dedic; Capaldo, Bajcetic, Clark; Nene, Yeo, Gloukh
Brest possible starting lineup:
Bizot; Lala, Coulibaly, Chardonnet, Amavi; Magnetti, Fernandes, Camara; Del Castillo, Ajorque, Sima
We say: Red Bull Salzburg 2-0 Brest
Salzburg are sure to seize the initiative in their first home game of the league phase, and their bunch of talented youngsters could overrun a struggling Brest side.