Diego Simeone's side, twice finalists in the competition in the last four years, are perennial continental contenders, and are among the favourites to go deep into the later rounds once again this season, despite having been unable to make any new signings over the summer due to a transfer ban.
A recent agreement between the two clubs over the sale of Diego Costa back to Atlético provides an intriguing sub-plot to Wednesday night's meeting, but the Brazil-born Spain international will not feature for either side as the switch cannot be completed until January.
Another La Roja striker, however, will be pivotal to Chelsea‘s hopes of returning to London with a positive result in the bag.
Álvaro Morata has been in outstanding form since his £65million signing from Atleti's bitter rivals Real Madrid, with six Premier League goals already, and he'd love nothing more than to be the first away player to score at the old enemy's new stadium.
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Atlético remain unbeaten in all competitions so far this season, and their trademark defensive rigidity has seen them concede just four goals in seven games.
Simeone may wish to stick with the partnership of Manchester United transfer target Antoine Griezmann and Luciano Vietto in attack, which saw Los Colchoneros beat Sevilla 2-0 at the weekend, although young Argentinian forward Ángel Correa has been in fine form so far this term and will be in contention to start.