There is no question that Lokomotiv will be wary of their opponents on Tuesday night having suffered a 5-1 loss on the last occasion that they hosted the Spanish giants. Indeed, Simeone's team ran out comfortable winners in their Europa League last-16 second leg during the 2017-18 campaign.
As mentioned, Lokomotiv recorded an impressive 2-1 victory away to Leverkusen in their Group D opener. Incredibly, it was the first time that they had managed to win an away game in the Champions League since the 2002-03 group stage.
This is the fifth time that the Russian side have been present in the group stage of the Champions League - they struggled last season, though, finishing bottom of a section which also included Porto, Schalke 04 and Galatasaray, losing five of their six group matches in the process.
What's more, Yuri Semin's side have won just five of their last 13 European fixtures in Moscow, while they have been victorious in only two of their nine home games against Spanish opposition.
It is a big ask to expect the hosts to qualify for this season's round of 16, but they are going well in the league this term - beating Zenit St Petersburg 1-0 on Saturday to sit third, just two points off leaders CSKA Moscow.
Atletico have made an encouraging start to the season, with a total of 14 points from their seven La Liga matches seeing them occupy third - one point behind leaders Real Madrid following Saturday night's tense goalless draw at the Wanda Metropolitano.
Simeone's side trailed 2-0 to Juve in their first Champions League group match on September 18, but Stefan Savic and Hector Herrera both scored in the final 20 minutes to secure a share of the spoils.
Atletico have actually reached two Champions League and three Europa League finals in the last 10 seasons, which is an indication of their standing in the European game. What's more, the Spanish giants have lost just three of their last 23 matches in European competition - recording 14 wins in the process.
Last season, the capital outfit progressed to the round of 16, where they suffered a 3-2 aggregate defeat to Juventus, who were seen by many as the favourites to win the European Cup last term.
Atletico have won on four of their six trips to Russia in European competition, meanwhile, remaining unbeaten in the process. Lokomotiv are sure to provide stern opposition on Tuesday night, but Simeone's side will be looking to pick up another positive result in the Russian capital.
Lokomotiv Moscow form: LWWWLW
Atletico Madrid form: WLDDWD
Thomas Lemar made his return from injury off the bench against Real Madrid, meanwhile, meaning that Simeone has plenty of options for change on Tuesday night, even with Vitolo expected to miss out due to a calf strain.
Lokomotiv Moscow possible starting lineup: Guillherme; Ignatyev, Howedes, Corluka, Rybus; Mario, Krychowiak, Murilo, Barinov, Zhemaletdinov; Smolov
Atletico Madrid possible starting lineup: Oblak; Trippier, Savic, Gimenez, Lodi; Koke, Llorente, Saul, Correa; Morata, Costa
We say: Lokomotiv Moscow 1-2 Atletico Madrid
Lokomotiv currently lead Group D heading into Tuesday's fixtures, but it would be a surprise if that was the case at the end of the next matchday. Games in Moscow are always tough for the visitors - Atletico know how to pick up results in these type of games, though, and we fancy the Madrid giants to triumph.
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