Undefeated Real have a one-point advantage over champions Barcelona after nine matches and have so far faced mainly mid- to lower-table opposition, scoring 19 goals in their last four outings.
Barca, who host Real at the end of the month, play at Getafe on Sunday having defeated Sevilla (5-0) and Valencia (2-1) at home. They also won 2-1 at Atletico, who are sixth in the standings.
Real goalkeeper and captain Iker Casillas said he and his team mates were highly motivated for the Atletico match after snatching a stoppage-time equaliser at AC Milan in the Champions League on Wednesday.
"We managed to avoid defeat in an important match and we want to carry on in the same vein," the World Cup winner said on Real's website.
Atletico are looking for a first win over Real for more than a decade and had a scare on Tuesday when Diego Forlan went over on his left ankle in training.
The Uruguay striker, who has been below his best since finishing joint top scorer at the World Cup, suffered a slight sprain but was included in the squad for Thursday's Europa League match against Norwegian side Rosenborg and came through a training session in Trondheim on Wednesday.
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Claudio Ranieri was the last Atletico coach to savour victory over Real when Jimmy Floyd Hasselbaink scored twice in a 3-1 away triumph in 1999.
Ranieri's successor, Quique Sanchez Flores, said it was to be expected that Forlan would have a dip in form after his exploits in South Africa.
"All the players who made a big effort at the World Cup have problems in the first few months of the domestic league season and we knew it was going to happen," he told a news conference.
"That's why we are trying to give him as much space and time as possible to recuperate."
Third-placed Villarreal host Athletic Bilbao on Sunday and Valencia, in fourth, play at eighth-placed Sevilla in the Monday game.
