Simeone's team will head to Real's Santiago Bernabeu ahead of their more fancied city rivals on the La Liga table but the Argentine coach does not expect the visitors to spend much time with the ball.
Atletico have a perfect record so far this season in La Liga with 18 points from six matches, while Real are two points adrift.
But Real, who Simeone described as 'a better team' than his own, will be expected to control the match, although that does not overly concern Atletico's boss.
Simeone believes Atletico have the counter-attacking ability to hurt Real.
"We'll have to give the 110 per cent, less will not be enough for us," Simeone said on Friday.
"They have great players that don't need much to make the difference. It will be complicated.
"We have to keep playing as we are, as an intense team and I also think Real's style will benefit us as I expect them to have the ball.
"So we'll have to focus on using our weapons."
In the last clash between these two teams, Atletico stunned Real 2-1 in extra-time to win the Copa del Rey.
It was Atletico's first win in 30 matches against Real but the breakthrough triumph has hardly changed Simeone's perception of the biggest club in Madrid.
"We face a better team than us with a great squad," the 43-year-old Argentine said.
"And if we don't give 110 per cent we won't have any chance.
"So let's be focused."
Get the best features, fun and footballing frolics straight to your inbox every week.
Thank you for signing up to Four Four Two. You will receive a verification email shortly.
There was a problem. Please refresh the page and try again.