Real Madrid and Barcelona must overcome tired legs going into this weekend's fixtures, with the two powerhouses of Spanish football bracing themselves for a fifth game in 14 days.
Real sits top of the Spanish table, with coach Jose Mourinho starting with 10 points from a possible 12, while Barcelona is a point behind in fourth place.
Madrid travels to promoted Levante on Saturday looking to retain top spot, although second-place Valencia is only below it on goal difference, with Mourinho admitting the grueling schedule of midweek games and Champions League is taking its toll.
"The team is tired because it still isn't a proper team and the coach doesn't use rotations," said Mourinho.
"I usually rotate four or five players successfully once my teams are constructed after years of work."
Mourinho has largely stuck by what he regards as his strongest XI, although Karim Benzema - a 30 million euro signing from Lyon - will hope for a chance after impressing as a goalscoring substitute in the midweek win against Espanyol.
Real begins as a strong favorite to win at Levante, although the league newcomer got its first points of the season on Wednesday with a 1-0 win at Almeria.
"We don't have a lot of time to recover between matches and we are facing a team (Levante) that don't have anything to lose," added Mourinho.
Barcelona coach Pep Guardiola has been rotating his squad, with Spanish World Cup winners Gerard Pique and Pedro Rodriguez rested for Wednesday's 1-0 win over Sporting Gijon.
The pair could be back for Saturday's tough trip to Athletic Bilbao.
Barca is high on confidence after three successive wins in all competitions, but Lionel Messi is still missing with an ankle injury and the hostile San Mames is traditionally one of the most difficult Spanish grounds for visitors.
"We have to rest and prepare for a great game on Saturday and go into the match convinced that if we do things well we can get a positive result against the best team in Europe," said Bilbao coach Joaquin Caparros.
Barcelona drew 1-1 at Bilbao last season and will be desperate not to drop points to stay in touch with Real at the top.
Spanish international striker David Villa, who scored the winner against Gijon, believes it is too early to focus on the league table, saying Barcelona had proven its mettle by winning four major trophies in the last two seasons.
"The difference between Barcelona and Real Madrid is obvious. You just have to look at the titles the team won in the last two seasons," said Villa.
"Barcelona did something no one had ever done before by winning six trophies (the Champions League, Spanish league, Kings Cup, European Super Cup, Spanish Super Cup and World Club Championship) in one year."
Villa's old side, Valencia, is level with leader Real on 10 points and travels to Sporting on Saturday looking to maintain its unbeaten start.
Atletico Madrid has taken one point from the last six to fall to sixth but entertains bottom side Real Zaragoza - with no wins to its name - at the Vicente Calderon on Sunday.
After losing its season opener to Real Sociedad, Villarreal has won its last three matches to go third, a point behind Real Madrid, and is targeting a fourth successive win at Malaga on Sunday.
Elsewhere, unbeaten Sevilla, down in fifth, travels to promoted Hercules on Sunday.
Hercules beat Barcelona 2-0 at Camp Nou to cause the upset of the season so far, but that remains its only victory on its return to the top flight.