Ten-man Valencia earlier made it three wins out of three and went clear at the top of the standings when Juan Mata and Pablo Hernandez scored in a 2-1 win at Hercules.
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Barcelona crashed to a shock 2-0 home defeat by promoted Hercules last weekend but spoiled Atletico's perfect start to the season with a much more accomplished performance at a typically boisterous Calderon stadium.
Messi, taken off on a stretcher in added time after a wild tackle from Tomas Ujfalusi damaged ligaments in his right ankle, poked Barca ahead in the 13th minute, seconds after a David Villa strike had ricocheted back off a post.
Atletico midfielder Raul Garcia lifted the crowd with a towering header past Victor Valdes in the 25th before Spain defender Pique outmuscled the home defence to put Barca back in front just after the half hour.
Atletico goalkeeper David De Gea kept the home side in the match with smart saves from Xavi and Pedro at the start of the second period and Villa and Messi both missed chances to make the game safe.
Villa blasted over with the goal at his mercy and Messi fired straight at De Gea when through on the keeper late on.
ROUSING OVATION
The Atletico fans gave Barca midfielder Andres Iniesta, scorer of the winning goal for Spain in July's World Cup final, a rousing ovation when he was replaced by Javier Mascherano.
However, Barca's victory, their first under Guardiola at the Calderon, was soured shortly after when Messi was carried off and the Argentina forward looked in some pain, clutching his face with both hands as he was stretchered around the touchline.
Czech defender Ujfalusi, who had already picked up a booking, was shown a straight red card.
Barca said in a statement on their website Messi had sprained the external ligament in his right ankle but there was no bone damage and further tests would be conducted on Monday.
Coach Pep Guardiola called the team's performance "spectacular" against an "aggressive and intense" Atletico.
"We are very pleased with the win but sad about the injury to Leo (Messi)," he added.
Unai Emery's Valencia, who kicked off their Champions League campaign with a resounding 4-0 win at Turkey's Bursaspor, took the lead in the second minute against Hercules when Spain international Mata volleyed in from a Hernandez centre.
Winger Hernandez doubled the visitors' lead in the 23rd before former Juventus striker David Trezeguet netted from the penalty spot for Hercules two minutes before the break.
Defender David Navarro was dismissed after picking up a second yellow five minutes into the second period but Hercules were unable to find an equaliser.
Valencia have nine points from t
