Atletico must take on Osasuna on Tuesday before travelling to the Santiago Bernabeu for the first time since beating their rivals at their own ground in the Copa del Rey final in May.
But Simeone believes his side, who have made a 100 per cent start to the new season, could struggle against Javi Gracia's men if their minds are not focused on the job at hand.
"We have to take each game as it comes, otherwise we’ll undo the good work done in beating Real Valladolid away from home," he said.
"If we didn’t get a good result at home, that wouldn’t be good. We have to take each game as it comes and keep growing."
Osasuna, who appointed Gracia following the sacking of Jose Luis Mendilibar in September, picked up their first points of the season courtesy of a 2-1 over Elche on Friday.
And Simeone is wary that the Basque club will now have "raised expectations".
"They’re a side that are dangerous out wide, with Emiliano Armenteros and Sisi providing a lot of pace," he explained.
"Their midfield will be packed out with players to win the ball back and come out of defence quickly. We have to keep a high tempo to the match and look for the intensity we need to keep moving forward."
Second-placed Atletico sit two points clear of Real in third, with both sides unbeaten in the league this season.
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