Champions Barcelona have received a massive boost with the return to fitness of Spanish international Andres Iniesta as the travel-weary Catalan side visit high-flying Getafe on Saturday.
While many Getafe players watched the international games on television, Barcelona's array of jet-setting stars played twice inside a matter of days and must now raise themselves again.
Barcelona can, however, count on the services of fit-again Iniesta, who has not played since the Champions League final win over Manchester United at the end of May, after suffering a torn thigh muscle.
"It's very important for the team to get Iniesta back because he's a unique player with great qualities," said Argentine defender Maxwell.
"He makes it all look so easy on the pitch and he can decide a game on his own.
"It's difficult to work when there are so many players away (on international duty) and maybe Getafe have the advantage but we aren't looking for excuses."
Getafe, who narrowly avoided relegation last season, currently lead the 20-strong table after a 4-1 win over Racing Santander, while Barcelona are second making it an early top of the table clash, although only Barcelona are expected to be near the top come May.
As well as vital league points the game is preparation for Barcelona's eagerly-anticipated Champions League group match at Inter Milan on Wednesday.
While Barca head to Madrid to face Getafe, Real go the opposite way to Barcelona to take on Espanyol.
It is the first competitive game at Espanyol's new Cornella-El Prat stadium and it should be one to treasure against Spain's most successful team.
"We are not going to change our style of play despite the quality of Real Madrid," promised Espanyol coach Mauricio Pochettino.
"We have to be solid at the back although it is difficult to stop the likes of Kaka, Cristiano (Ronaldo) and (Karim) Benzema because they have the individual quality and are capable of the unexpected."
Real's multi-million euro Galacticos laboured to a 3-2 win over Deportivo La Coruna in the season curtain-raiser that showed Real's attacking threat but also a defensive fragility that was often exposed last season.
"We have only just started and the squad has once again, undergone a large metamorphosis and there have been a lot of changes," explained goalkeeper Iker Casillas.
"It is normal that we have still things we need to work on, however, as we play more games, I am certain that we will become more co-ordinated," he said.
No-one knows how long it will take Real to really click but expectations are sky high and patience is not the forte of the demanding Madrid fans.
Atletico Madrid supporters already appear to have lost their patience just one game into the new season and are planning a protest at their lack of activity in the transfer market during Saturday's home match against Racing Santander.
Atletico ended last season on a high with Champions League qualification but failed to follow it up with any big name signings and lost their opening game 3-0 at Malaga.
"I don't know the motivation behind the (planned) demonstration, but I hope that it is to thank us for keeping (our) great players - something that very few clubs in Europe were able to do," said Atletico president Enrique Cerezo.
Sevilla were another Champions League participant to get off to a bad start with a loss against rivals Valencia so they look for their first points of the season at home to promoted Real Zaragoza on Saturday.
Valencia's trio of David Villa, David Silva and Juan Mata all played a key role in Spain's recent World Cup qualification and Valencia hope they can maintain their stellar form for Sunday's trip to Valladolid.