Real Madrid head into the fourth Madrid derby of the season at Atletico on Sunday following their 6-1 thrashing of Schalke in the Champions League and buoyed by the return of Cristiano Ronaldo.
After losing 1-0 at home to Atletico in La Liga back in September, Real gained revenge over their local rivals with a comprehensive 5-0 aggregate win in the semi-finals of the Copa del Rey earlier this month.
Carlo Ancelotti's men have also usurped Atletico in the league in recent weeks.
Los Rojiblancos' shock defeats to Almeria and Osasuna have allowed Real to open up a three-point lead over both Atletico and Barcelona at the top of the table.
Real will be further boosted by the return of Cristiano Ronaldo to league action after the Ballon d'Or winner missed his side's last three domestic games for his red card and dissent shown in their 1-1 draw away to Athletic Bilbao on February 2.
The Portuguese captain returned in customary fashion, scoring twice as Real all but secured their place in the last eight of the Champions League with their demolition of Schalke, and he is looking to channel his frustration at the length of the ban to good effect this weekend.
"What's done is done. I am frustrated about it because what I did wasn't deserving of a three-game ban, but I am happy to return and score two goals," he said.
"We are motivated for the derby, we are Real Madrid and we will give everything to win."
Atletico, meanwhile, should be refreshed by a rare midweek off as they aim to put a run of four defeats in six games behind them.
Midfielder Koke recognised the task that faces his side at the Vicente Calderon, but insisted that even in Real's current form no side is invincible.
"You always like to play against Madrid, above all if you can beat them. It is a derby, which is always a special game," he told the club's website.
- 'No-one is invincible' -
"No one is invincible in this world. Defensively they are very good and in attack they have important players with excellent individual skills. We are facing a great team and we will try to do everything as best we can. It will be a great game."
With one or both sides from the capital set to drop points, Barcelona can take advantage when they host Almeria at the Camp Nou on Sunday.
The Catalans were also blown away last weekend when they lost 3-1 at Real Sociedad to finish the weekend behind Real Madrid for the first time since 2012.
However, with Barca still to face Real at the Santiago Bernabeu on March 23, Cesc Fabregas believes his side are still capable of retaining their title.
"We are the first ones to know that we didn't play well. We lacked mobility, intensity and precision, which are vital things in modern day football," the midfielder said.
"We have analysed it, we know where we failed and now we have to recover all that we lost there.
"It is in our own hands. I believe a lot in this squad and these players, as much for what they have done in the past as their present. We are ready to do something great this season."
Fabregas and Xavi are expected to be recalled to the side after they were controversially rested by coach Gerardo Martino against Sociedad.
Javier Mascherano will also return to the heart of the defence alongside Marc Bartra as Gerard Pique faces a brief spell on the sidelines due to a calf injury.
Fixtures (all times GMT)
Athletic Bilbao v Granada (1930)
Malaga v Valladolid (1500), Levante v Osasuna (1700), Getafe v Espanyol (1900), Elche v Celta Vigo (2100)
Villarreal v Real Betis (1100), Atletico Madrid v Real Madrid (1600), Sevilla v Real Sociedad (1800), Rayo Vallecano v Valencia (2000), Barcelona v Almeria (2000)