Madrid coach Jose Mourinho faces the loss of up to seven of the 19 players who went off on international duty after the vital 2-2 draw with Barcelona in their last league game.
It’s a problem which has left “los blancos” the main victims of what the Spanish press have dubbed the “Fifa virus”.
Despite the draw against Barcelona at Camp Nou two weeks ago, Madrid still have an eight-point gap to make up on their Catalan rivals, a task made even more difficult by the loss of so many key defenders.
Right-backs Alvaro Arbeloa, injured in Spain’s 1-1 draw with France and Fabio Coentrao are unavailable for a number of weeks while left-back Marcelo is expected to be out for three months after breaking his foot in a Brazil training session.
Midfielder Sami Khedira and forwards Karim Benzema and Gonzalo Higuain picked up knocks with their national sides and all could be rested ahead of an important Champions League tie at Borussia Dortmund next Wednesday.
Mourinho will have to be creative to fill the full-back berths.
Michael Essien has experience on the right while Sergio Ramos could also be used there with Raphael Varane or Raul Albiol coming into the centre of defence.
Even using Varane is in doubt after the youngster picked up a muscle injury while playing for the French Under-21 side.
Youngster Nacho Fernandez could make his first start of the season at left-back.
Leaders Barcelona have few worries as they go to Deportivo La Coruna on the same evening, looking to make it four wins from four on the road.
One player unaffected by the international break was midfielder Andres Iniesta.
“I didn’t play the full 90 minutes of the two matches with Spain so I’m in good shape, my (groin) injury is forgotten and we all hope to be fit for the Depor game which will be complicated especially after the break,” he said.
“There’s a long way to go, all sides go out to win games, particularly Madrid who are the current champions and they will want to win the title again so we can’t take the points for granted,” he said.
“Also we have to concede that at the moment Atletico Madrid are our closest rivals.”
On Sunday, Atletico face a tough away game at Real Sociedad who have won their three home games to date this season.
Atletico are level with points with Barca at the top and eight ahead of city rivals Real.
But their Turkish midfielder Arda Turan is another victim of the international break and will miss Sunday’s game along with Diego Costa who has a troubled knee.
Raul Garcia is the likely replacement for Turan while Atletico will look to the rich goalscoring form of Gustavo Falcao to continue a run of nine straight victories in all competitions since the opening day 1-1 draw at Levante.
Malaga v Valladolid
Real Madrid v Celta
Valencia v Athletic Bilbao
Deportivo v Barcelona
Getafe v Levante
Espanyol v Rayo Vallecano
Granada v Zaragoza
Osasuna v Betis
Real Sociedad v Atletico Madrid
Sevilla v Mallorca