De la Hoya had planned a comeback to the ring with a fight on Sept. 11 at Staples Center after more than a decade away.
But the boxer posted a video to Instagram from his hospital bed, saying even though he's been vaccinated he is struggling with a COVID-19 infection.
Oscar de la Hoya discusses COVID-19 infection, withdrawal from comeback fight
"What are the chances of me getting COVID?" he says in the video. "I've been taking care of myself. This really, really kicked my ass."
Former heavyweight champion Evander Holyfield, who similarly hasn't fought for a decade, has agreed to step in and box Belfort in his place.
That fight still needs to get approved by the California State Athletic Commission.
RELATED: De la Hoya talks about motivation for returning to the ring
If it isn't, the promoter is eyeing a move to Florida.