Barcelona have been careful to break new recruit Neymar in gently during the opening weeks of the Primera Division season and Real Madrid are likely to follow a similar policy with Gareth Bale, even with several key players carrying injuries.
Football’s richest club by income, who like champions Barca have a perfect nine points from three matches, splashed a record $133 million to secure Bale's services and he could make his debut at promoted Villarreal in Saturday's late kickoff .
The 24-year-old winger played the final half hour of Wales's 3-0 World Cup qualification defeat at home to Serbia on Tuesday, his first competitive action since July, and coach Chris Coleman warned afterwards it would be unwise for him to play a full match this weekend considering his relative lack of fitness.
Saturday 14 September
Atl Madrid v Almeria
Levante v Real Sociedad
Barcelona v Sevilla
Villarreal v Real Madrid
Saturday 15 September
Granada v Espanyol
Getafe v Osasuna
Malaga v Rayo Vallecano
Real Betis v Valencia
Monday 16 September
Elche v Valladolid
At Bilbao v Celta de Vigo
After arriving in the Spanish capital on Wednesday, Bale had his first workout with his new team mates and although Real have a number of players injured, coach Carlo Ancelotti is unlikely to deploy him from the start at the Madrigal.
Portugal winger Cristiano Ronaldo, Spain playmaker Isco and Brazil fullback Marcelo all returned from international duty with problems of varying degrees of seriousness.
Ronaldo and Isco trained apart from the rest of the squad on Wednesday, while Marcelo had treatment from medical staff along with long-term absentee Xabi Alonso.
Villarreal, along with Atletico Madrid the only other team to win their opening three games, are eager to test themselves against opponents of Real's calibre after spending a year in the second division last term.
Under coach Marcelino they have shown real attacking flair and their performances so far this term suggest they are more likely to be challenging for a place in Europe than flirting with relegation come the end of the campaign.
"It's a chance to show that we can compete with anyone and that we can fight against a team like Madrid," captain Bruno Soriano told a news conference on Wednesday.
"Last year, we were dreaming about playing these teams and now the opportunity has arrived and we want to put in a great performance," the midfielder added.
"Personally I prefer it if an opponent is at full strength and that the best come so we can take them on.
"Although even if Madrid has some players out, I am sure they will have the same level of quality."
Barca are waiting on the fitness of midfielder Sergio Busquets and fullback Daniel Alves as they prepare to host Sevilla on Saturday.
Coach Gerardo Martino has used Neymar sparingly in the early stages of Barca's title defence, although he did play 90 minutes of the 3-2 victory at Valencia in their last league outing before the international break.
The Brazil forward shone for his country in friendly victories against Australia and Portugal over the past week, scoring a goal in each game including a trademark sprint through the Portuguese defence followed by a clinical finish.
Barca's World Player of the Year Lionel Messi also returned on Wednesday after helping Argentina secure qualification for next year's World Cup in Brazil with two penalties in a 5-2 success in Paraguay.
Messi missed the 1-0 win at Malaga last month before notching a hat-trick at Valencia to take his tally for the season to five goals in two games including a double at home to Levante in the opening round of matches.
Atletico, who are at home to promoted Almeria on Saturday, made a couple of new signings this month, bringing in Belgium defender Toby Alderweireld from Ajax Amsterdam and France midfielder Josuha Guilavogui from St Etienne.
Fellow Champions League participants Real Sociedad, who lost 2-1 at home to Atletico in their most recent outing, play at Levante, also on Saturday.