Barcelona - Real Madrid will hope Cristiano Ronaldo's return from suspension will be enough to overcome a spate of injuries when it visits Atletico Madrid on Saturday in another rematch of last season's Champions League final.
James Rodriguez joined Madrid's list of injured players when he broke a bone in his right foot on Wednesday. Sergio Ramos is also likely to be out after injuring his leg.
Coach Carlo Ancelotti will have to look to his bench to field a starting 11 against an Atletico side that has bettered his team in three competitions this season.
While Madrid leads the league with Atletico seven points behind in third, second-place Barcelona enters the weekend four points behind the pacesetters and will wait until Sunday to visit Athletic Bilbao.
Here are some things to know about the 22nd round of matches:
Madrid's 2-1 win over Sevilla on Wednesday proved costly when both Rodriguez and Ramos went down in the first half.
Rodriguez was set to have surgery on Thursday, while the club was still waiting to determine the extent Ramos' thigh injury.
Madrid was already without midfielder Luka Modric (left leg) and defender Pepe (ribs).
Marcelo also saw his fifth yellow card against Sevilla. Ancelotti said the club would appeal the booking and that he will rely on center backs Raphael Varane and Nacho Fernandez to anchor his defense.
"We lose some experienced heads but sometimes an injection of enthusiasm is a good thing," Ancelotti said. "I'm not worried."
The derby at Vicente Calderon Stadium will be the sixth time the city rivals have met since Madrid prevailed 4-1 in extra time in May's Champions League final.
Diego Simeone's Atletico has yet to lose to Madrid in five meetings since, beating them in the league, the Copa del Rey and the Spanish Super Cup.
"We know our rival well," said Atletico midfielder Tiago Cardoso. "I don't think coach will change much. We will try to play strong in a tight unit and take advantage of our chances."
Ronaldo will return from a two-match suspension for kicking a Cordoba player.
Ronaldo, who turned 30 on Thursday, leads the league with 28 goals, but he hasn't shown the same brilliant form since he won his third Ballon d'Or award in early January.
Neymar's two sides
Barcelona's victory in the bidding war to sign Brazil striker Neymar in 2013 has proven to be a good investment on the pitch and a headache off it.
This week a judge named club president Josep Bartomeu a suspect in an ongoing investigation into Neymar's contract, alleging Bartomeu defrauded Spain's Tax Office of 2.8 million euros ($3.2 million).
Neymar, however, has become a superb strike partner for Lionel Messi.
Neymar, who turned 23 on Thursday, is the team's second-leading scorer behind Messi. He has 22 goals in 26 appearances this season, well above his total of 15 goals in his first campaign.
Messi has scored nine goals during Barcelona's seven-game winning streak, with Neymar right behind with eight.