But after Mayweather extended his unbeaten record to 48-0 Saturday night with a unanimous-decision victory over Pacquiao at MGM Grand, a dispute over a denied injection Pacquiao said he needed for his pained right shoulder cast a cloud over the long-anticipated bout between the world's top two boxers.
A miscommunication involving Pacquiao's promoter, Top Rank Inc., the Nevada State Athletic Commission and the fight's drug-testing supervisor, the U.S. Anti-Doping Agency, prevented Pacquiao from receiving an injection containing the anesthetic lidocaine and two other pain-relieving prescription medications.
On April 4, Pacquiao suffered a twisted right shoulder when he and a sparring partner tangled while each threw overhand rights. Two days later, he was examined, and a tear underneath the rotator cuff in a joint was found, and he was given a cortisone shot to alleviate the pain, said his manager, Michael Koncz.
The injury limited Pacquiao's ability to train with his right hand. In an interview at his hotel suite Sunday, Pacquiao said he went into the fight with his right arm functioning at 60%.
But Pacquiao's camp was told by his orthopedist that he could take the injection if he wanted, and USADA approved the in-competition use of the remedy in a document.
The problem was that USADA never shared its approval with the state commission, Chairman Francisco Aguilar said Sunday, and when Pacquiao's camp told the commission it wanted the fighter to take the injection at 6:08 p.m. on fight night, the request was rejected.
Aguilar said that Pacquiao's camp noted the possible need for the lidocaine cocktail on a medical form filled out at Friday's weigh-in, but a check mark in the "no" box was placed next to the question of whether the fighter had a shoulder injury.
"If the injury was disclosed at the weigh-in, we could've had a conversation and handled it differently," Aguilar said. "When you come at 6:30 with the fight at 8, that's a different conversation."
Pacquiao was still seething over the rejection Sunday.
"I'm so disappointed," he said.
Pacquiao will have his shoulder examined in Los Angeles on Monday and could undergo surgery in the Philippines that will sideline him three to six months. He said he "almost" sought a postponement of the Mayweather bout when he suffered the injury.
He said he pressed to keep the date after so many failed opportunities because he knew the injection would be available. He brought two doctors with him to his dressing room Saturday night.
Holding his arm in a sling-like manner under his jacket Sunday, telling visitors he was incapable of shaking hands, Pacquiao said he re-aggravated the injury while dominating the fourth round.
He couldn't produce the performance he wanted afterward as Mayweather remained in his brilliantly elusive form. Pacquiao resorted to pursuing one knockout punch with his left that never came.
"It felt like a needle was being stuck into my shoulder," he said.
The defense-minded Mayweather actually out-punched the frequent-punching Pacquiao, winning on judges' scorecards, 118-110, 116-112, 116-112.
"I backed off because of the pain," Pacquiao said. "It's very important to have confidence in your right and left, and when you're hurt, you're thinking about that, too."
Koncz said, "Floyd gave a masterful performance, and Manny was diminished greatly."
Pacquiao's injury before the momentous event that will shatter boxing revenue records brought his promoter, Bob Arum, under scrutiny for knowing his fighter was hurt and keeping the date rather than rescheduling the fight and letting him heal, which the fight contract allowed.
Koncz said, "If Manny told me to stop the fight, I'd have stopped it, but he's not going to do that. He said he'd be letting the fans down, that he'd be OK with the shot.
"In my opinion, the promoter works for the boxer. What comes first? Staging an event or protecting the fighter?"
Said Arum: "Athletes always fight hurt. We felt he had the opportunity to use the right hand. We were disappointed the injury kicked up, but this is always the case with sports. A guy is injured in training, deals with it, thinks he's conquered it, then gets re-injured in the game."
Mayweather, meanwhile, announced after the victory that he will relinquish all five of his world-title belts, to allow younger fighters to pursue them. He also said he'll fight for a final time in September.
England's Amir Khan is the most likely foe should he beat Chris Algieri later this month.
Pacquiao said he wants to fight again and retains hope for another shot at Mayweather, who might be swayed to give him one after he cashes the $100-million check he received Saturday and collects an even greater figure in pay-per-view revenue.
Las Vegas opens a new arena in 2016, an opportunity, perhaps, for Mayweather to top Rocky Marciano's 49-0 record at retirement. Mayweather wouldn't discuss a rematch after his triumph.
"For years, all you guys said I was scared [of Pacquiao]," Mayweather told reporters in his post-fight news conference. "Write your stories [now], and I'm going to wake up early in the morning and see what you all wrote. … I turned all the non-believers into believers."