Even De La Hoya believes the fight is likely to be the sport's last great matchup for years - quite an admission, since he has a thriving career selling fights as a promoter.
Still, he's not ready to write off boxing.
"This is not a dying sport," said the 34-year-old De La Hoya, whose partners expect him to fight again after Saturday night. "There are still big fights here, big fights in England, big fights in Germany. The sport is alive and well. It's just a matter of making good fights, and the people will come. Boxing is never going anywhere."
Though the national spotlight shined on De La Hoya and Mayweather for several weeks, boxing is a shaky shadow of the cultural force it once was. Its popularity has waned for more than two decades, blasted for its barbarism and corruption while other contact sports - from football to mixed martial arts - are thriving.
"I don't think we'll have the big mega-events for quite a while," De La Hoya said. "We'll have great events always, but I don't think we'll have the same big mega-events. That's the big challenge to us as promoters. Boxing will take a hit, I understand that."
So where does that leave Bernard Hopkins and Winky Wright, who have the unenviable task of meeting each other in the next big fight after the Big Fight?
Both veteran champions, who'll fight in Las Vegas on July 21, are convinced the sport can stay relevant as long as people enjoy watching other people hit each other - and as long as boxing keeps cleaning up its act and promoting its stars to provide a show casual fans can understand and enjoy.
"We have a product that people want to see, but we've got to make it the best it can be," said Hopkins, a partner in De La Hoya's promotions company. "We're doing some of the right things with Golden Boy Promotions, and we've got to keep doing it. But there's no doubt we're at a crossroads. This thing could get bigger, or it could go away."
Boxing's problems are well documented - from the loss of top athletes to other sports and the absence of glamorous heavyweights to the ridiculous sanctioning bodies and weight classes that confuse even the fighters themselves.
There's also a direct drain on the sport: Boxing has lost much of its cultural importance to the octagon of ultimate fighting, with its clear organization and consistent television presence along with its fresh martial arts spin.
But De La Hoya believes anybody who has been near ringside knows few events can match the electricity and anticipation of a prizefight.
The sport still makes millions in pay-per-view buys every year, including well over a million customers for De La Hoya-Mayweather, and millions more at the gate. Most of the big-name fighters still in the ring are 30 or older - but that's not a bad thing. De La Hoya, Mayweather, Hopkins and Wright all are experienced and wealthy enough to handle their own fight promotions, rather than entrusting their fates to the Don Kings of the world. De La Hoya, Hopkins and partner Richard Schaefer run Golden Boy Promotions, which claims its fiscal openness can encourage sponsors to return to a sport long regarded skeptically by the business world. "I think the single weakest link in boxing is the lack of sponsorship support, and that's where we've really focused as a company," said Schaefer, who inked traditional boxing sponsors such as brewers and energy-drink makers along with first-time partners such as Southwest Airlines for De La Hoya-Mayweather. Schaefer also said HBO plans to make another documentary leading up to the Hopkins-Wright fight similar to "De La Hoya/Mayweather 24/7," the critically praised four-part series that concluded Thursday night after introducing many casual fans to both fighters' day-to-day lives. The internecine squabbles among promoters, managers and fighters have long prevented top fights from occurring with any regularity. Boxing is still too jumbled to match the UFC's organization, but the sport's top minds believe teamwork could keep the excitement in boxing long after De La Hoya and Mayweather are done. "We hope this fight motivates everybody in the sport to have the best fight against the best," said Mark Taffet, the senior vice president of HBO Sports. "That's what we've all got to work towards. The fans will support the sport of boxing if we continue to do what we're doing (with De La Hoya-Mayweather). The fans will support us if we give them what they want."