Atletico Madrid return to Real Madrid's Santiago Bernabeu home on Saturday for the first time since breaking their 14-year drought in the Madrid derby back in May.
Diego Simeone's men won the Copa del Rey in their rival's own backyard 2-1 after extra time in an action-packed encounter that saw Real's star man Cristiano Ronaldo and then manager Jose Mourinho sent off.
Mourinho has since been replaced by Carlo Ancelotti on the Real bench, but Atletico's revival under Simeone continues unhindered as they currently lead their city rivals by two points in La Liga having won all six of their matches to date.
Victory over Osasuna on Tuesday meant Atletico equalled their best ever start to a league season and they are looking to continue their sensational form in the biggest game either side has faced so far this season.
"We know we can win and we know how to beat them. We have managed to do it now," said Atletico defender Filipe Luis.
"We know it is still going to be very difficult, even when having an off day in the cup final, they had six or seven clear chances and hit the post a few times.
"But our team is very solid, we have a spectacular collective level and we need to maintain that with the spirit that no one is more important than anyone else."
Gareth Bale is expected to finally make his home debut for Real after a thigh strain forced him to pull out of last weekend's 4-1 win over Getafe in the warm-up.
And with Luis likely to go head-to-head with the Welshman, he is aware of the challenge that awaits him.
"I think that the best thing for the spectacle is that everyone is available and able to play.
"Bale is a very good player, but Real Madrid have the fortune to be able to count on Bale or Di Maria, who also cost 40 million, or Isco, who cost I don't know how much.
"Whoever plays it is obvious Bale is a fantastic player. I have never played against him, but I know it will be difficult to stop him."
Diego Costa will be the biggest threat to Real with his seven goals in six league games so far rumoured to have the naturalised Brazilian on the verge of a call-up to the Spanish national team.
And the hosts will have to substantially improve on their showing against Elche in midweek as only a controversial injury time penalty converted by Ronaldo prevented them from dropping four points behind Atletico and Barcelona.
"Obviously playing like this we are not going to win the derby," a furious Ancelotti admitted after his side's 2-1 victory.
"We need to play with more intensity and personality."
Marcelo could also return to the Madrid side after missing the last few weeks in place of Fabio Coentrao at left-back.
And the Italian must decide which two from Asier Illarramendi, Luka Modric and Sami Khedira will start in midfield.
Barcelona have the chance to open up an advantage at the top of the table when they travel to Almeria earlier on Saturday.
The Catalans looked back to their fluent best in a 4-1 destruction of Real Sociedad on Tuesday and victory would also seal their best ever start to a league campaign.
However, there are defensive concerns for coach Gerardo Martino as Javier Mascherano has joined Jordi Alba on the sidelines.
The inexperienced Marc Bartra is likely to deputise for the Argentine as club captain Carles Puyol is still well short of match fitness after successive knee surgeries in March and June.
Valladolid v Malaga (1800GMT)
Valencia v Rayo Vallecano (1400GMT), Almeria v Barcelona (1600GMT), Real Sociedad v Sevilla (1800GMT), Real Madrid v Atletico Madrid (2000GMT)
Osasuna v Levante (1000GMT), Celta Vigo v Elche (1500GMT), Espanyol v Getafe (1700GMT), Real Betis v Villarreal (1900GMT)
Granada v Athletic Bilbao (1900GMT)