Early-season pacesetters Atletico Madrid play host to two-time reigning Primera Division champions Barcelona in what promises to be another titanic encounter between the two at the Vicente Calderon this weekend.
Atletico are riding the crest of a wave at present having finished last season by winning the Europa League and reaching the final of the Copa del Rey and then starting the current campaign with a European Super Cup win over Inter Milan and back-to-back victories in La Liga.
Those two triumphs have left Quique Sanchez Flores' side at the top of the Primera Division standings, level on six points with Valencia, and optimism will be growing in the Rojiblancos camp that they can push the big two of Real and Barca hard this season.
This weekend, therefore, offers Atletico the perfect chance to showcase their credentials with mighty Barca the visitors.
The two clubs have been involved in some epic battles in recent seasons, with the last seven league meetings between the two producing 39 goals.
In that time Barca have enjoyed some thumping wins over the Rojiblancos, including 6-0, 6-1 and 5-2, but Atletico have won their last three home games against the Catalan outfit, scoring 10 times and conceding five.
Barca midfielder Andres Iniesta, whose side suffered a shock 2-0 home defeat to promoted Hercules last weekend but bounced back with an impressive 5-1 Champions League mauling of Panathinaikos in midweek, said of this weekend's trip to Atletico in Marca: "It will be difficult.
"Last season it was the only game we lost. They are an opponent who are historically uncomfortable for us and we will have to try to do things well to have a chance of breaking this bad run.
"It's important not to give them any chances. They have great players and are in good form. Currently they are one of the best teams in Europe."
Atletico have a question mark over the fitness of key striker Sergio Aguero, who has a leg injury that ruled him out of Thursday's Europa League clash at Aris Thessaloniki.
Real Madrid will look to continue their steady progress under new coach Jose Mourinho when they make the trip to last season's Segunda Division champions Real Sociedad on Saturday.
Having drawn 0-0 with Real Mallorca in their opening league match and then beaten Osasuna 1-0 last weekend, Madrid saw off Ajax 2-0 in their first Champions League match in midweek.
Madrid should really have scored an avalanche of goals against the outclassed Dutch side, but poor finishing and good goalkeeping meant they were limited to just the two.
Mourinho is unconcerned though, saying: "One day some poor team will pay for all these chances we've missed.
"If we only had two shots I would worry, or if (goalkeeper Iker) Casillas was our best player, but in the last three matches he has not touched the ball."
Like Barca and Real, joint-Primera Division leaders Valencia also enjoyed a successful start to their Champions League campaign as they thumped Bursaspor 4-0 in Turkey. Unai Emery's side take on Barca's conquerors Hercules this weekend.
While Hercules bask in the glory of their shock Camp Nou win, the third promoted side, Levante, go into their home match with neighbours Villarreal having lost both their opening two league matches 4-1.
That has left the Valencia-based team bottom of the standings, with Racing Santander - who face fourth-bottom Real Zaragoza - the only other team yet to pick up a point.
Malaga, who scored five times in the opening 34 minutes en route to beating Zaragoza 5-2 away last weekend, host third-placed Sevilla in what could be an intriguing Andalusian derby.
In this weekend's other games, Espanyol host Almeria, Osasuna go to third-bottom Real Mallorca, Sporting Gijon are at home to Athletic Bilbao and Getafe are at Deportivo La Coruna.