Coach Carlo Ancelotti will seek to bolster Madrid's league lead on Sunday against Quique Sanchez Flores' 14th-placed team that has won just four matches in 18 rounds.
Atletico, meanwhile, faces bottom of the league Granada that has managed to win two matches all season.
Barcelona travels to lowly Deportivo La Coruna on Sunday.
Here are some things to know about this weekend's matches as La Liga reaches its midpoint:
Sergio Ramos acknowledged Madrid's defense needed to improve after making errors that led to Atletico's Copa victory, but emphasized his team's desire to win the league.
"Now we want to recover and focus on the remaining competitions," Ramos said. "We are going to do everything possible to win the Champions League and La Liga,"
However, Madrid will be without Pepe against Getafe after the key defender bruised his ribs during the second half of the Copa match.
Madrid leads the standings on 42 points after 17 rounds, with a game in hand because of its December participation in the Club World Cup. The postponed 16th-round fixture against Sevilla will be held Feb. 4 at the Bernabeu.
Fernando Torres overshadowed Cristiano Ronaldo's third Ballon d'Or celebrations at the Bernabeu by scoring both of Atletico's goals in its second-leg 2-2 Copa draw Thursday (4-2 on aggregate).
Both goals came from inspired passes by 23-year-old France forward Antoine Griezmann, who Torres says will get even better.
"We have to let Griezmann grow, you have to enjoy things with him and make him feel like an important player, because he is," Torres said. "We all know he has a great future and as a teammate, we need to enjoy with him, to help him so he can make all of us grow. I will help him every way I can."
Atletico hosts Granada on Sunday.
Barcelona coach Luis Enrique saved his attacking trio of Lionel Messi, Neymar and Luis Suarez for the league match at the Riazon stadium, having secured a 5-0 first leg win in the Copa that the Catalan powerhouse won 9-0 on aggregate Thursday.
Enrique will hope his squad plays like it did last weekend during its 3-1 defeat of Atletico in order to maximize its chances of closing the gap to Madrid. Messi has scored 16 of his 25 goals this season in the league.
In preparation for the tough clash, Deportivo this week reinforced its midfield with Costa Rica playmaker Celso Borges who helped the central American country reach the quarterfinals at World Cup in Brazil last summer.
Coach Victor Fernandez's team is one point above the relegation zone.
UPS AND DOWNS
Villarreal hosts Athletic Bilbao on Saturday, with the teams seemingly heading in opposite directions.
Villarreal has risen to sixth place in the league and reached the knockout stages of the Europa League.
It also advanced to the final eight of the Copa del Rey after knocking out Real Sociedad on Wednesday when it extended its unbeaten run in all competitions to 14 games.
Bilbao, however, is struggling under coach Ernesto Valverde and its fans jeered the team after its 2-0 loss to Celta Vigo on Wednesday, even though it advanced in the Copa on away goals.
That came after a 2-1 home loss to lowly Elche in its last league match, extending a winless streak in the league to five rounds.
"I see it as normal and necessary, it's good that our fans demand more of us," Valverde said of the jeers. "We have to change our mindset and take a step forward."
OUT OF CREDIT
Granada hasn't won in the league in 14 straight games, a drought that stretches back to Sept. 20.
Its fortunes aren't likely to change when it visits the Vicente Calderon Stadium on Sunday.
Granada, which was ousted from the Copa del Rey following a 4-0 rout at Sevilla on Wednesday, has scored a league-low 11 goals in 18 rounds.
Coach Joaquin Caparros has managed to keep his job largely thanks to his reputation as being one of the best at getting the most out of a limited squad.
But his credit is running low with his team in last place.
"We have to recover our spirits," said Caparros. "We can't drop our heads. We still have the entire second half of the season to go and we need to be convinced that we are going to pull this out and transmit that to our fans."
Associated Press writer Joseph Wilson contributed to this preview.