Lionel Messi scored twice as a second-half substitute to help a short-handed Barcelona win 4-1 at Getafe on Saturday as the Spanish pacesetters remained perfect through the league's opening four rounds.

With Andres Iniesta and others out with injury, Barcelona turned to Cesc Fabregas to lead the attack, and he responded by setting up Adriano for the 32nd-minute opener.

Messi went on with half an hour to play and scored a penalty in the 74th and the third goal in the 78th to decide the contest and take his league-leading tally to six.

Getafe pulled one back before David Villa, still finding his form after returning from a broken leg, went on for Barcelona and scored in injury time with a classy effort reminiscent of his pre-injury level of play.

Meanwhile, Defending champion Real Madrid fell eight points behind Barcelona after falling to Sevilla 1-0.

Madrid, which has won just once in four rounds, was unsettled at the start at Sanchez Pizjuan Stadium and Piotr Trochowski capitalized to score from a corner two minutes in, breaking Sevilla's streak of seven straight defeats to Madrid.

Madrid coach Jose Mourinho was scathing of his players after their second league loss.

"We got what we deserved after a horrible game," said Mourinho, who will have to find some quick answers before their Champions League opener against Manchester City in just three days.

"My players' heads are not focused, for many of them football is not a priority. But I am the coach, and if there are heads that are not focused it is my fault.

"I am not worried about the points, my worry is that I don't have a team."

All eyes were on Madrid forward Cristiano Ronaldo to see if he would again refuse to celebrate his goals in a display of his unexplained displeasure with his club.

But Sevilla's defence made sure the Portugal forward never got the chance to show his "sadness" with another glum display.

Mourinho denied that Ronaldo's enigmatic comments in the last round about not being happy at Madrid, which have sparked speculation that he is seeking a new contract or even a transfer, had rattled his squad.

"No, I don't think so. This game wasn't very different from the other games," he said. "Therefore I don't think it has any relation with the rumour of the last two weeks."

Madrid was unnerved from the start and left Trochowski free to charge into the area and blast Ivan Rakitic's cross into the top of the net.

Mourinho shuffled his lineup at halftime with Luka Modric and Karim Benzema going on.

"At halftime I changed two players, but I wanted to change seven," Mourinho said.

Modric made his presence felt with a long-range strike that goalkeeper Andres Palop grazed just enough to alter its trajectory and send it crashing off the upright.

But Madrid's apparent renewal turned into a mirage as it again stalled in attack down the stretch.

Also, Valencia beat Celta Vigo 2-1 and Malaga downed Levante 3-1 before their respective Champions League openers against Bayern Munich and Zenit St. Petersburg.

Messi started the game in southern Madrid on the bench after a long international week with Argentina and Barcelona's own Champions League opener against Spartak Moscow set for Wednesday, adding to the void left by the injured Iniesta, Alexis Sanchez and Jordi Alba.

Despite its depleted frontline, Barcelona dominated the ball and soon found its rhythm in attack.

Thiago Alcantara, playing his first minutes since May due to injury, almost scored for the visitors in the 26th after using some nimble footwork to dribble by two defenders, only to send his shot off the crossbar.

But Fabregas cued Barcelona's opener when he carried the ball into the area, shed one defender and laid off for Adriano to score in his second straight game following the Brazilian defender's winner last round.

Barcelona's injury problems continued to grow in the second half, however, when Carles Puyol was substituted in the 57th after hurting his left knee.

Getafe, which beat Madrid here at Alfonso Perez Stadium two rounds ago as well as Barcelona last season, looked for the equalizer with occasional flashes of danger.

Assistant coach Jordi Roura, in charge of Barcelona with Tito Vilanova completing his two-game suspension, sent Messi on in the 59th and he quickly put the result beyond doubt.

The star forward converted a spot kick after Pedro Rodriguez was tripped by Juan Valera in the area, and four minutes later Messi tapped in a cross by Martin Montoya after a friendly deflection off a defender.

Getafe got its consolation goal in the 80th when Pablo Sarabia's shot ricocheted off both Adriano and Javier Mascherano before falling into the net.

But Villa sealed the rout after going on 15 minutes before time when he collected a pass and shot by Moya.