Diego Simeone's side are seeking to emulate last season's run to the final of Europe's premier club competition and will be favourites to progress against their Bundesliga opponents.
Ahead of the opening meeting between the sides in Leverkusen, Simeone spoke of his respect for Roger Schmidt's men and highlighted the importance to Atleti of keeping possession.
"It's a huge match for us. We want to keep control of the game and also keep possession of the ball," said Simeone in his pre-match media conference.
"But we have to be careful. If we're in possession, Leverkusen will apply a lot of pressure to get the ball back.
"We're in very good shape and are really enthusiastic. But we have to be very focused – this is always very important for our performance. If we do that, we get a good result.
"Leverkusen has a good team structure and a great coach. It's always important to show respect to your opponents.
"I don't know if teams give us more respect now just because we've done well in the past.
"There may be more attractive opponents than us, who you would rather face, but we're here. I don't think we're the favourites in this tie. It starts at 0-0 so anything is possible."
Atletico forward Saul hinted that a cautious approach could be adopted by the Spanish champions on Wednesday.
"It will be important to keep a clean sheet. We value having the second leg at the Calderon," he said.
"We were very eager for the Champions League to return. It's a competition we like and we're excited."
Enjoy your first month for just £1 / $1 / €1
*Read 5 free articles per month without a subscription
Try your first month for just £1 / $1 / €1