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It was the second loss in a row for Pacquiao, who dropped a decision to Timothy Bradley in June and who had vowed to regain his prominence in the ring.

Pacquiao was aggressive from the opening bell, but paid the price in the third round when he got caught by a Marquez right hand that put him down. Pacquiao got back up and seemingly took control of the fight, dropping Marquez in the fifth round and landing the bigger punches until he was dropped.

“I got hit by a punch I didn’t see,” Pacquiao said.

Pacquiao, who earned more than $20 million for the fight, was ahead 47-46 on all three scorecards after the fifth round.

There was no title at stake in the 147-pound fight, but that didn’t stop 16,348 fans from filling the MGM Grand Arena and roaring in unison from the opening bell as the two fighters went after each other.

Ringside punching stats underscored the ferocity of the bout, showing Pacquiao landing 94 of 256 punches to 52 of 246 for Marquez. But it was the one big right hand from Marquez that counted more than anything, knocking Pacquiao out for the first time in a career that goes back 17 years.

“He was in charge,” Pacquiao’s trainer, Freddie Roach said. “He just got a little too careless and got hit with a punch he didn’t see.”

Promoter Bob Arum immediately said he could see a fifth fight between the two boxers, and a dazed Pacquiao seemed to agree.

“Why not?” he said.

Pacquiao weighed the class limit of 147 pounds, but it was Marquez who looked like the stronger fighter entering the ring after having bulked up with the help of a strength conditioner, though he weighed in at 143 pounds. In their earlier fights, Pacquiao had been the bigger puncher, knocking Marquez down a total of four times, but on this night it was Marquez who had the biggest punch.

The stunning knockout was the first real loss by Pacquiao in seven years. He lost a close decision to Bradley in his last fight, but most ringside observers believed he had won it fairly convincingly.

Marquez improved to 55-6-1 with 40 knockouts, while Pacquiao fell to 54-5-2.