The visitors will arrive at the Vicente Calderon having not won in their last four games, a run that has seen them complete three goalless draws.
In contrast, Simeone's Atletico have only lost once in their last eight and they will be expected to claim three points and keep the pressure on city rivals Real at the top of La Liga.
Nevertheless, the Argentinian insists Atletico cannot take anything for granted.
He told reporters: "We will see how it goes. It is clear that we will need a strong start, and look at how to hurt the other team, who come here on the back of three really good matches, defending really well.
"That has to make us more focused and see if they play with five in the back and three in the middle, or with four like they have done sometimes."
Simeone is confident his side can deliver, adding: "I think the team is improving and growing. The team work has been maximized, making individuals shine more. And that is what makes us happy.
"When the team grows, the individuals are stronger. Thanks to this teamwork, we can see a team keeping regularity, the most difficult thing in the game."
