Having been drawn alongside Bayern Munich and Atletico Madrid in Group A, both sides are aware of the importance of the game at the Red Bull Arena.
While Red Bull Salzburg are regarded by some as a stepping stone towards eventually representing RB Leipzig or another top European club, the Austrian outfit have proven in recent years that they can match some of the best sides on the continent.
Since reaching the Europa League semi-finals in 2017-18, Die Roten Bullen have remained on an upward trajectory, and they pushed Liverpool and Napoli in thrilling encounters in last season's group stages.
However, at a time when their star players continue to be linked with high-profile moves, Jesse Marsch will be targeting a first-ever appearance in the knockout stages of this competition.
There can be no doubting that they remain as underdogs to achieve that goal, but scoring 17 goals in their first four league matches this season suggests that they have already hit form.
Patson Daka, a player wanted by many of the clubs in the Premier League, has contributed five strikes and three assists during those fixtures.
While Salzburg needed to defeat Maccabi Tel Aviv to progress through to the group stages, Lokomotiv earned their spot through second place in Russia's top flight.
Marko Nikolic's side have endured a mixed start to the campaign, recording six wins and three draws from their 11 league fixtures to currently sit in fourth position.
However, they have recently put together a four-match winning streak, a run which has included a derby success against rivals CSKA Moscow.
Goals remain a problem, though, with Fedor Smolov the only player to have netted more than twice on the domestic scene this season.
Lokomotiv suffered five defeats in last season's group stages, finishing bottom of a group which featured Juventus, Atletico and Bayer Leverkusen.
Red Bull Salzburg Champions League form: WW
Red Bull Salzburg form (all competitions): WWWWWW
Lokomotiv Moscow form (all competitions): DDWWWW
Marsch heads into this game with only Andre Ramalho missing from his Salzburg squad.
The Austrian side should line up in a 4-4-2 formation with in-demand Dominik Szoboszlai taking his place on the left flank.
Daniil Kulikov is in line to come into the centre of midfield at the expense of Stanislav Magkeev.
Red Bull Salzburg possible starting lineup:
Stankovic; Vallci, Onguene, Wober, Ulmer; Okugawa, Camara, Mwepu, Szoboszlai; Daka, Koita
Lokomotiv Moscow possible starting lineup:
Guilherme; Zhivoglyadov, Corluka, Cerqueira, Rybus; Kulikov, Krychowiak; Zhemaletdinov, Miranchuk, Rybchinsky; Smolov
We say: Red Bull Salzburg 2-1 Lokomotiv Moscow
Taking their domestic form into consideration, it appears that these two teams are evenly matched. However, while Lokomotiv will look to keep things tight during the opening stages of the game, we feel that Salzburg should have enough quality in the final third to ultimately secure maximum points.