Champions Real Madrid make the short trip to Getafe on Sunday knowing that even at such an early stage as the season's second weekend, a win is vital.
Bitter rivals Barcelona already have a two-point advantage after their opening day 5-1 thrashing of Real Sociedad.
While Madrid could only draw 1-1 at home to Valencia, they were fortunate to come away from Camp Nou with a 3-2 defeat to Barcelona on Thursday night in the Spanish Super Cup first-leg.
Coach Jose Mourinho admitted that Barca were the stronger side on the night and will be looking for a winning performance on Sunday against neighbours who lost their first league outing 2-1 at Sevilla.
Barca also have a tricky trip to Osasuna but will have Alex Song and David Villa available to start their first games of the season.
Villa came on as substitute and scored against Sociedad in his first game since last December when a broken leg finished his season.
Song is yet to feature since his 19-million-euro signing from Arsenal.
For Madrid, Mourinho will again have the luxury of choosing between Karim Benzema or Gonzalo Higuain to partner Cristiano Ronaldo in attack.
Benzema started on Thursday against Barcelona while Higuain scored his side's first goal of the season against Valencia last weekend.
Jonas Goncalves, who got Valencia's goal in the Bernabeu, is convinced that his side can improve on last season when they finished third in the league and reached the Europa League and Spanish Cup semi-finals.
"We are working towards going a step further than last season, we have began with a lot of desire and we have to keep that going all season," he said.
Valencia host a Deportivo La Coruna side on Sunday night that had their own positive start to the campaign with a 2-0 win over Osasuna.
One of a number of Deportivo players making his debut for the club in that game was Spanish World Cup winner and ex-Valencia player Carlos Marchena who is looking forward to his return to Mestalla.
"It will be special for me, it's a place in which I spent a lot of time and they treated me very well, but I'm returning with another club that has its own interests so all of those positives will be forgotten on the pitch," he said.
"Valencia has changed so much since I was there, the coach (Mauricio Pellegrino) was then one of my colleagues and he will give the side the character and discipline it had when I played there," he added.
Atletico Madrid and Athletic Bilbao will close the second round of games on Monday in a repeat of last season's Europa League final.
There was some good news for Bilbao on Thursday when they managed a 6-0 win in their Europa League tie with Helsinki amid turbulent times at the club as the future of star players Javi Martinez and Fernando Llorente remain unclear.
Despite losing 5-3 at home to Betis on the first weekend of the season, Atletico coach Diego Simeone expects a difficult game against the Basque side.
"They will be competitive and their current problems will not stop them. They are strong and work hard, I expect to meet the strongest possible Athletic side, the same as last season," he said.
Real Sociedad v Celta (1700 GMT), Betis v Rayo Vallecano (1900 GMT), Espanyol v Zaragoza (1900GMT), Malaga v Mallorca (2100 GMT)
Osasuna v Barcelona (1700 GMT), Granada v Sevilla (1900 GMT), Getafe v Real Madrid (1900 GMT), Valencia v Deportivo (2100 GMT)
Valladolid v Levante (1800 GMT), Atletico Madrid v Athletic Bilbao (2000 GMT)