Las Palmas make their first visit to the Santiago Bernabeu for 13 years on Saturday hoping to avoid the same punishment they received in a 7-0 thrashing on their last trip to the capital.
The Canary Islanders have already changed their coach just nine games into their return to the top flight as Paco Herrera was sacked despite guiding them to promotion.
Quique Setien got off to a promising start with a 0-0 draw at home to Villarreal last weekend, which at least moved Las Palmas off the bottom on goal difference, but is aware of the dauting task that faces his side at the Bernabeu.
"Real Madrid are a team that doesn't need to play well to win," he said on Thursday.
"They have the players to resolve a game in any moment. It will be a difficult game, but during this season we have seen other teams cause them problems and have chances to take something from the game."
Rafael Benitez remains unbeaten as Madrid boss 12 games into his tenure and should have the luxury of welcoming back a host of injured stars who have been absent in recent weeks.
James Rodriguez, Karim Benzema and Pepe could all feature having returned to training this week, but Gareth Bale misses out once more due to a calf problem.
With Madrid and Barcelona tied on 21 points at the top of the table, a Real victory can take them clear for a few hours at least before Barca face Getafe later on Saturday.
The Catalans only managed a 0-0 draw at the Alfonso Perez Coliseum last season and are again debilitated by injuries and suspensions.
Javier Mascherano joins injured Argentine international teammate Lionel Messi on the sidelines due to a two-game ban for being sent-off against Eibar last weekend.
Brazilian duo Rafinha and Douglas are long-term injury absentees, while midfielders Andres Iniesta and Sergi Roberto face a race against time to be fit.
"Statistically, I think Barcelona have never been comfortable coming to the Coliseum," Getafe midfielder Pedro Leon told the club's website.
"There have been all sorts of results and we hope that on Saturday we can make it as difficult for them as possible and get a positive result."
- Simeone cautious -
Atletico Madrid have the chance to usurp the big two and go top for just short of 24 hours when they travel to Deportivo la Coruna on Friday night.
Los Rojiblancos produced their best performance of the season in beating Valencia 2-1 last time out, but coach Diego Simeone doesn't want his talented young squad to get ahead of themselves.
"We always live for the next game. We have spoken with the team about leaving the past behind us and concentrating on what we do on Friday," said the Argentine.
"Every game is a new world and people will value what you are going to do, not what you have done."
Simeone is expected to name the same starting line-up for the first time in 47 games despite an energy-sapping near 6,000 kilometre trip to face Kazakh champions Astana in the Champions League to come on Tuesday.
Sevilla have the chance to continue their upturn in form and make up lost ground on the top four caused by a poor start to the campaign when they travel to Villarreal on Saturday.
Villarreal still hold a five-point lead over Sevilla and Valencia in the battle between the three most likely candidates for the fourth Champions League place, but the Yellow Submarine have taken just one point from their last three games.
Valencia are in badly in need of a win to ease the pressure on coach Nuno Espirito Santo when they host Levante in the Valencia derby.
Meanwhile, Celta Vigo can put David Moyes's position as Real Sociedad coach back under serious scrutiny should they bounce back from their first defeat of the season against Real Madrid last weekend with victory at Anoeta.
Fixtures (all times GMT)
Friday
Deportivo la Coruna v Atletico Madrid (1930)
Saturday
Real Madrid v Las Palmas (1500), Villarreal v Sevilla (1715), Valencia v Levante (1715), Getafe v Barcelona (1930), Real Sociedad v Celta Vigo (2105)
Sunday
Eibar v Rayo Vallecano (1100), Espanyol v Granada (1500), Sporting Gijon v Malaga (1715), Real Betis v Athletic Bilbao (1930)
Source: AFP
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