Champions Barcelona face one of their toughest remaining fixtures in the title run-in on Saturday with a testing trip to third-placed Villarreal.
Barca, five points ahead of Real Madrid at the summit, have struggled after international games in the past and coach Pep Guardiola will hope his heavy-legged stars can pick themselves up for a key game at El Madrigal.
A proposed strike had threatened to see this weekend's round of games cancelled over a row over broadcast regulations and television money, but a Madrid court ruled in favour of six breakaway clubs to avert the strike.
Barcelona have defensive concerns with Carles Puyol injured and Frenchman Eric Abidal recovering following surgery to remove a liver tumour.
Top scorer Lionel Messi is also doubt with a leg injury that prevented him from playing in Argentina's friendly against Costa Rica.
The champions may not want to risk their star man ahead of Wednesday's Champions League quarterfinal first leg against Shakhtar Donetsk.
Real Madrid have also had a number of stars away on international duty and are without Brazilian Marcelo and French forward Karim Benzema for Saturday's home match against Sporting Gijon.
Benzema, who has seven goals in his last four league matches, picked up a thigh injury on international duty with France and faces a race to be fit for Tuesday's Champions League quarterfinal first leg against Tottenham Hotspur at the Santiago Bernabeu.
Real coach Jose Mourinho will not want to take risks ahead of that game and Cristiano Ronaldo is also likely to miss out against Gijon with the hamstring injury that ruled him out of Portgual's recent games.
Real have a 100 per cent record at home but Sporting, three points above the relegation zone, are fighting for their lives and possess a motivated coach in Manolo Preciado.
Preciado had a war of words with Mourinho earlier in the season, calling the Portuguese egotistical after Mourinho said Gijon gave in too easily in their 1-0 league loss against Barcelona in late September.
It is an intense month for Madrid and Mourinho, who face Barcelona twice, in the league and King's Cup final, as well as two Champions League quarterfinal matches against Tottenham.
FIXTURES
Saturday
Real Madrid v Sporting Gijon (1600GMT), Getafe v Valencia (1800GMT), Villarreal v Barcelona (2000GMT)
Sunday
(1500GMT unless otherwise stated)
Real Sociedad v Hercules, Espanyol v Racing Santander, Levante v Malaga, Deportivo La Coruna v Real Mallorca, Sevilla v Real Zaragoza (1700GMT), Osasuna v Atletico Madrid (1900GMT)
Monday
Almeria v Athletic Bilbao (1900 GMT)