The Argentina international failed to score against the Spanish champions during his five-year stint at Real's local rivals.
"Never defeating Real when I was with Atletico was a real regret for me," The Express quotes Aguero as saying. "Atletico haven't succeeded in beating them for many years but I did get to score against them even if we never managed a win.
"This game will hopefully break that run for me. It's always special to play against a club like Real. Personally, my connection with Atletico gives it an additional kick."
City are unlikely to qualify for the knockout rounds of the European competition after picking up just two points throughout the campaign.