Barcelona and Atletico Madrid look to extend their club record starts to the season when they host Valladolid and Celta Vigo respectively this weekend.
Both sides have won all seven of their league matches to date and could set a new Spanish record should they make it eight out of eight.
The Catalans have the chance to open up a three-point gap at the top of the table as they play first on Saturday night.
Gerardo "Tata" Martino's men continued their fine start to life under the Argentine by also making it two wins from two in the Champions League in midweek with a hard-fought 1-0 success over 10-man Celtic.
Young defender Marc Bartra particularly impressed in Glasgow as he continues to deputise for the injured Javier Mascherano and he is thankful for the confidence Martino has showed in him.
"Tata has not doubted for a second in putting me into the team. I am satisfied with the confidence he has shown in me," he told a press conference on Thursday.
"Little by little I am feeling more wanted. I have had two years competing with some of the best players in the world in training and learning from them.
"I have keep concentrating and learning."
The champions will have to do without World Player of the Year Lionel Messi as he is sidelined with a thigh injury.
Mascherano and Jordi Alba are also unavailable through injury, but Barca's defence could receive a significant boost with the return of captain Carles Puyol to the squad for Saturday's match.
The 35-year-old hasn't played since undergoing knee surgery in March but has trained with his teammates in recent weeks and could make a return in the week that marked 14 years since his debut.
Real Madrid are also in action on Saturday as they travel to Levante needing to bounce back from last weekend's 1-0 defeat to Atletico which left them five points off the leaders.
Gareth Bale is once again unavailable due to a thigh strain, but Argentine winger Angel di Maria showed he is more than a capable replacement for the Welshman with two goals and a stunning assist in Real's 4-0 win over FC Copenhagen on Wednesday.
Coach Carlo Ancelotti's defensive options have also been swelled by the return of Raphael Varane and Marcelo from injury, but Sergio Ramos will certainly start after being rested in midweek.
Atletico also continued their 100 percent start in the Champions League thanks to a come from behind 2-1 win away to Porto on Tuesday that owed much to Diego Simeone's men's expertise from set-pieces.
Simeone will be able to welcome back top-scorer Diego Costa, who missed the game in midweek due to suspension, whilst Koke will also return having been rested from the start against Porto.
And Koke insists his side won't be taking anything for granted despite the plaudits they have received in recent weeks.
"We take all the compliments calmly and they give me even more confidence and desire to keep working. That confidence I am showing on the pitch," he told the club's website.
"It will be a difficult game against Celta because we are coming form two very demanding games. The group is physically and mentally prepared and we are desperate to go for the three points."
Elsewhere, Valencia will be hoping to extend their four-match winning run when they travel to face Athletic Bilbao in a meeting between Champions League contenders on Sunday night.
However, Athletic will also fancy their chances having won both matches since moving into their new San Mames stadium last month.
Friday Villarreal v Granada (1800GMT), Malaga v Osasuna (2000GMT)
Saturday Elche v Espanyol (1400GMT), Rayo Vallecano v Real Sociedad (1600GMT), Levante v Real Madrid (1800GMT), Barcelona v Valladolid (2000GMT)
Sunday Atletico Madrid v Celta Vigo (1000GMT), Sevilla v Almeria (1500GMT), Getafe v Real Betis (1700GMT), Athletic Bilbao v Valencia (1900GMT)