The 13th round of games in La Liga and the last before the third and final international break before Christmas kicks off with Athletic Club Bilbao entertaining Cadiz in the San Mames Stadium.
A win will lift Athletic right into the battle for European places and while Cadiz travel third from bottom of the table without a win in their last seven games.
Granada's win away to Levante on Monday gave Robert Moreno some breathing space ahead of Saturday's visit to Cornella to face Espanyol, who will have Raul de Tomas back in their starting 11 after he missed last weekend's defeat to Getafe due to suspension.
Sergi Barjuan will remain in the Barcelona dugout for their visit to play Celta Vigo, although with talks to contract Xavi Hernandez advancing, it could be the B-team coach's last game at the helm.
Barca's 1-0 win at Dynamo Kiev on Tuesday kept their Champions League hopes alive, but with the team sitting ninth in La Liga, they need all three points from their visit to a misfiring Celta.
Kun Aguero is out for at least three months as investigations continue into his irregular heartbeat, but the loss of the striker is somewhat offset by the return of Ansu Fati, who scored the vital goal on Tuesday, and Ousmane Dembele, who will be able to offer pace and balance on the right.
Meanwhile Sergi Roberto, Pedri, Gerard Pique and possibly Sergino Dest will all miss out due to injury.
Alaves' point in the Camp Nou last weekend was another sign of their recovery as they have claimed seven points from a possible nine to climb out of the bottom three. That recovery can become definitive if they defeat Levante on Saturday afternoon.
Levante are second from bottom and their recent change of coach doesn't seem to have worked with Javier Pereira taking just two points from his first four matches in charge. There is even a chance that another defeat for Pereira could see him out of the club after just a month as coach.
Real Madrid were booed off the pitch by a section of their fans after their 2-1 win at home to Shakhtar Donetsk on Wednesday and although coach Carlo Ancelotti said that was not a bad thing as it will provoke a reaction. The Italian will probably make changes with players such as Eduardo Camavigna given a chance in the starting 11. Gareth Bale and Rodrgyo are injured and it remains to be seen if Eden Hazard gets some game time.
Villarreal coach Unai Emery rejected the chance to move to Newcastle during the week and he now needs his team to pick up their league form after three defeats and a draw from their last four games. Getafe are the visitors and travel with their morale boosted after last weekend's first win of the campaign.
Atletico Madrid need to recover from their 2-0 Champions League defeat to Liverpool when they visit Valencia in what promises to be a bruising game, before Mallorca entertain Elche.
The last two games of the weekend are both derbies with Osasuna at home to league leaders Real Sociedad who will hope to have Mikel Oyarzabal back after injury, before Betis take on Sevilla in the Seville derby.
Betis go into the most hostile derby in Spain fifth in the table, while Sevilla sit third - level on points with Real Madrid and both sides' positive start to the campaign will only add to the tension and competition in a match which rarely ends with 22 players on the pitch.