The Federal Bureau of Prisons confirmed Epstein's death, saying he was found unresponsive in his cell at New York's Metropolitan Correctional Center around 6:30 a.m. ET.
Staff started life-saving measures, and Epstein was taken to a hospital, where he was pronounced dead, the bureau said in a news release.
No foul play is suspected in his death, a federal official told CNN. The bureau's release called it "an apparent suicide," and said the FBI is investigating. Authorities believe Epstein hanged himself, one of the law enforcement sources said.
The New York City medical examiner's office hasn't determined his manner of death.
Epstein had been jailed since early July, when he pleaded not guilty to charges by New York federal prosecutors after an indictment accused him of sex trafficking dozens of underage girls, some as young as 14 years old.
News of Epstein's death comes a day after hundreds of pages of court documents were unsealed in New York federal court, alleging new details of sexual abuse claims against Epstein and several associates.
US Attorney General William Barr said Saturday that he was "appalled" to learn Epstein died of an apparent suicide in federal custody. The Justice Department's inspector general will investigate the circumstances of his death, Barr said.
"Mr. Epstein's death raises serious questions that must be answered," Barr said in a news release. Separately, a source familiar with the situation said Barr was livid at the events surrounding Epstein's apparent suicide and is determined to get to the bottom of what happened.
A spokeswoman for the US Attorney's office in Manhattan, which was prosecuting Epstein, declined to comment on Saturday.
An attorney for Epstein, Reid Weingarten, didn't immediately respond to a request for comment.
He was put on suicide watch after July injuries
Just weeks ago, Epstein was placed on a suicide watch after he was found July 23 in his Manhattan jail cell with marks on his neck, a law enforcement source and a source familiar with the incident told CNN at the time.
It's not immediately clear whether he still was on suicide watch at the time he died.
It was not clear in July to jail officials if the injuries Epstein sustained at that time, which were not serious, were self-inflicted or the result of an assault, the sources said. Epstein told authorities he was beaten up and called a child predator, they said.
July indictment followed 2007 plea deal
Epstein was officially accused, in part, of paying girls as young as 14 to have sex with him at his Upper East Side Manhattan home and his estate in Palm Beach, Florida, between 2002 and 2005.
Federal prosecutors said he used employees and associates to lure the girls to his residences and then paid some of his victims to recruit other girls for him to abuse.
He was awaiting trial on charges of trafficking of minors and conspiracy to engage in sex trafficking.
A federal judge in mid-July ordered Epstein to remain in jail pending trial, turning down the multimillionaire's request to return to his Upper East Side mansion under supervision.
Epstein faced similar accusations in Florida in 2007 but signed a plea deal that year with Miami prosecutors allowing him to avoid federal charges and plead guilty to lesser state prostitution charges.
The new charges renewed attention on the plea deal, spurring outrage against it and leading to the resignation of Trump administration Labor Secretary Alex Acosta, who negotiated the plea agreement when he was the US attorney in Miami.
Civil lawsuits could continue
Though criminal charges won't be pursued against a deceased defendant, accusers still could file civil lawsuits seeking money from Epstein's estate, CNN legal analyst Paul Callan said.
"(Epstein's) estate, you can imagine, would be sued by a lot of potential victims. So, his suicide will not end coverage and the interest in the Jeffrey Epstein case," Callan said.
One such lawsuit is expected to be filed as soon as Wednesday by a woman who alleges Epstein raped her when she was 15. Wednesday is the day that New York's Child Victims Act goes into effect, giving adult survivors of child sexual abuse one year to sue an abuser for offenses in New York, no matter how long ago the abuse took place.
The accuser in that pending lawsuit, Jennifer Araoz, said Saturday that she is "angry Jeffrey Epstein won't have to face his survivors of his abuse in court."
"We have to live with the scars of his actions for the rest of our lives, while he will never face the consequences of the crimes he committed the pain and trauma he caused so many people," she said in a prepared statement.
"Epstein is gone, but justice must still be served. I hope the authorities will pursue and prosecute his accomplices and enablers, and ensure redress for his victims," Araoz said.
Robbie Kaplan, an attorney for an accuser in the criminal case, said Saturday that "the many victims of Jeffrey Epstein and his accomplices should not lose hope."
"We will continue to fight tirelessly on their behalf not only to seek justice, but also to ensure that all of the facts of his monstrous crimes become known to the world," he said. "... We need to expose the whole truth here so that crimes of this scale and scope never happen to any young girls (or boys) ever again."