Villarreal, led by Spain international Gerard Moreno, will provide a sterner test for the champions, who have started the season slowly.
Barcelona were held to a frustrating goalless draw in the opening week by Getafe, then Pedri Gonzalez only breaking the deadlock as the clock ticked down against Cadiz.
However, the midfielder has been ruled out for the coming month with a thigh injury, depriving Xavi Hernandez and his side of a key creative player.
New arrival Ilkay Gundogan created Pedri's goal and has been bedding in well for Barcelona, as has 16-year-old starlet Lamine Yamal, but veteran striker Robert Lewandowski has struggled at the start of the season.
The 35-year-old Polish forward has not scored and looked disconnected from the team, leading him to drop back in search of the ball.
"He will score. He needs more patience," said Xavi after the narrow Cadiz win.
"The one he touches will be in his correct place -- (players) want to come deep, I understand, but you can't lose your position."
If Lewandowski is not at his best, it may put a lot of pressure on the shoulders of youngster Yamal, who filled in for the suspended Raphinha last weekend and impressed, although Ferran Torres, who netted the second goal against Cadiz, is also hoping to start.
"(Yamal) is very well prepared. He's very mature despite his age," said Xavi last week.
"He's a player who can make the difference, and that's not easy at Barça as a 16-year-old, I think he's ready to help the team."
Villarreal are without explosive winger Yeremy Pino, who is recovering from injury, but Moreno and new signings Alexander Sorloth and Ben Brereton Diaz have the quality to trouble Barcelona's defence.
Barcelona are still aiming to sign a right-back and, with Ronald Araujo injured, used Frenkie de Jong as a makeshift centre-back against Cadiz.
League leaders Real Madrid play early, visiting Celta Vigo on Friday night.
The Galicians are celebrating their centenary this week and will be aiming to cause an upset.
However, with Madrid's new arrival Jude Bellingham starting brilliantly - scoring three goals and providing an assist in his first two games - Carlo Ancelotti's side are a daunting prospect.
Rayo Vallecano, who like Los Blancos boast a 100 per cent record, welcome Atletico Madrid on Monday in a capital derby clash, while the other "perfect" team, Valencia, host Osasuna.
Player to watch: Pepelu (Valencia)
New arrival Pepelu netted from the penalty spot for Valencia in their win over Las Palmas next week and has been cementing himself as the heartbeat of Los Che, who will look to extend their 100 per cent record against Osasuna.
Key stats
3 - Real Madrid's Bellingham leads the scoring charts after hitting the ground running
8 - Real Betis' Abner has more blocks than any other player in the league
100 - Celta Vigo celebrated their centenary this week
