Lokomotiv could go above Atletico Madrid with a win, while the Rojiblancos will want to keep pace with Group A leaders Bayern Munich who are five points ahead of them.
Diego Simeone's men come into the game on the back of a hugely-impressive win over Barcelona, after having defeated Cadiz 4-0 prior to the break.
Yannick Carrasco found the net for Atletico Madrid in the final moments of the first half to give the Rojiblancos a 1-0 win at home, leaving them three points away from leaders Real Sociedad with two games in hand.
After getting hammered 5-1 in a Moscow derby against Dynamo prior to the international break, Lokomotiv Moscow resumed their winning ways with a 1-0 win over minnows Arsenal Tula, despite Vedran Corluka getting sent off at half time.
Anton Miranchuk scored from the spot midway though the second half to grab a fortuitous win for the hosts, ending a run of six games without a win.
Atletico Madrid vs Lokomotiv Moscow Head-to-Head
Atletico Madrid are unbeaten in their six games against Lokomotiv, winning four and drawing two. The Rojiblancos did the double over their Russian opponents in last year's Champions League group stages, winning 2-0 home and away.
The two teams last met earlier this month, playing out a 1-1 draw in Moscow, as Jose Gimenez's 18th-minute opener was cancelled out by Anton Miranchuk's 25th-minute penalty strike.
Atletico Madrid form guide: W-W-D-W-W
Lokomotiv Moscow form guide: L-L-D-L-W
Atletico Madrid vs Lokomotiv Moscow Team News
Diego Simeone will be without Uruguayan pair Luis Suarez and Lucas Torreira, who tested positive for the coronavirus while on international duty. Sime Vrjsalko and Hector Herrera continue to occupy the treatment room, with a return only possible in mid-December.
Given how crucial this fixture is, Simeone will most probably not rotate the lineup which defeated Barcelona, especially with an extra day of rest versus their opponents.
Injuries: Sime Vrjsalko, Hector Herrera
Covid-19: Luis Suarez, Lucas Torreira
Marko Nikolic has plenty of walking wounded to deal with, with Boris Rotenberg, Dmitri Barinoc and Mikhail Lysov out for the long-term. Stanislav Magkeev picked up a hip injury prior to the international break and has not recovered.
Fedor Smolov is also injured for this game, with Eder likely to replace him in attack. Vedran Corluka is sure to start as he is suspended domestically.
Injuries: Boris Rotenberg, Dmitri Barinoc, Mikhail Lysov, Fedor Smolov
Doubtful: Stanislav Magkeev
Atletico Madrid vs Lokomotiv Moscow Predicted XI
Atletico Madrid Predicted XI (4-4-2): Jan Oblak (GK); Kieran Trippier, Jose Gimenez, Stefan Savic, Mario Hermoso; Marcos Llorente, Koke, Saul Niguez, Yannick Carrasco; Angel Correa, Joao Felix
Lokomotiv Moscow Predicted XI (4-4-2): Guilherme (GK); Dmitri Zhivoglyadov, Slobodan Rajkovic, Vedran Corluka, Maciej Rybus; Vladislav Ignatiev, Grzegorz Krychowiak, Daniil Kulikov, Anton Miranchuk; Eder, Ze Luis
Atletico Madrid vs Lokomotiv Moscow Prediction
Despite the absence of Luis Suarez, Atletico Madrid can count on Joao Felix's terrific form for the club, with the Portuguese star likely to trouble the slow-paced Lokomotiv defence.
Diego Simeone knows this match will decide the fate of qualification and will be gunning for all three points, with Lokomotiv striker Eder unlikely to get any joy from Atleti's miserly backline.
Prediction: Atletico Madrid 2-0 Lokomotiv Moscow