The Italian giants appeared on course for an impressive victory away to Atletico when they moved into a 2-0 lead at the Wanda Metropolitano, only for Diego Simeone's side to salvage a draw with two goals in the final 20 minutes.
There was bigger disappointment for Leverkusen, though, as they slumped to a 2-1 defeat at home to Lokomotiv Moscow - a match which on paper at least should have been their easiest of the group stage.
Here, Sports Mole looks at how Maurizio Sarri could set his side out for the visit of the German outfit.
As is always the case, most eyes will be on Champions League top scorer Cristiano Ronaldo for this match, with the five-time winner of this competition hoping to open his European account for the season.
The Portuguese superstar returned from a minor thigh injury to score against SPAL at the weekend and could be joined up front by Gonzalo Higuain on Tuesday night, with Paulo Dybala in support having seemingly worked his way into Sarri's thinking.
Danilo's injury forced Sarri to deploy Juan Cuadrado as an emergency right-back on Saturday and the former Chelsea winger may need to carry out that role again in this match.
Behind him, Wojciech Szczesny should regain the gloves after dropping out to be replaced by Gianluigi Buffon last time out, the veteran surpassing Paolo Maldini's Italian record by playing in his 903rd club appearance.
Matthijs de Ligt should be handed a reunion with Leverkusen boss Peter Bosz, who handed him his senior debut at Ajax in 2016, while the likes of Aaron Ramsey and Adrien Rabiot may have to settle for a place on the bench.body check tags ::