Attorney General William Barr said in a statement Saturday that he was "appalled" to learn of the death and the Inspector General would open an investigation into the circumstances of his death. The FBI is also investigating.
"Mr. Epstein's death raises serious questions that must be answered," he said. "In addition to the FBI's investigation, I have consulted with the Inspector General who is opening an investigation into the circumstances of Mr. Epstein's death."
The 66-year-old Epstein was found unresponsive inside his cell at the Metropolitan Correctional Center in New York City around 6:30 a.m. Life-saving measures were initiated immediately by responding staff. He was transported to the New York Presbyterian-Lower Manhattan Hospital and was dead on arrival, officials said.
Law enforcement sources told Fox News that the initial call to the jail was cardiac arrest. Multiple reports claimed that he hanged himself. An autopsy is pending.
Marc Fernich, one of Epstein's attorneys, blamed the government, the judge in the case and the media for this "unthinkable tragedy."
"All these actors appear to bear some responsibility for this calamity. All seem to have a share of Mr. Epstein’s blood on their hands. All should be ashamed of their behavior," he said in a personal statement to Fox News. "I call for a full investigation into the circumstances surrounding Mr. Epstein’s death. The public needs to know exactly what happened and why — and how his custodians could have let it occur.”
Epstein's death comes two weeks after the 66-year-old was placed on suicide watch after he was found nearly unconscious in his cell with injuries to his neck. At the time, it was not clear whether the injuries were self-inflicted or from an assault.
He had been taken off suicide watch before he killed himself, a person familiar with the matter told the AP. It wasn't immediately clear when he was taken off suicide watch.
Epstein was arrested on July 6 over the alleged sexual abuse of dozens of young girls in his Upper East Side townhouse and his waterfront mansion in Palm Beach, Florida, between 2002 and 2005
Epstein allegedly created and maintained a “vast network” and operation from 2002 “up to and including” at least 2005 that enabled him to “sexually exploit and abuse dozens of underage girls” in addition to paying victims to recruit other girls. Prosecutors said that victims would be escorted to a room with a massage table where they would perform massages on Epstein.
At the time of Epstein's arrest, prosecutors said they found a trove of pictures of nude and seminude young women and girls at his $77 million Manhattan mansion. They also say additional victims have come forward since the arrest.
He had pleaded not guilty and faced up to 45 years in prison if convicted.
His death also comes a day after thousands of documents were unsealed Friday in connection with a defamation case against his alleged recruiter that revealed dozens of high-profile names including former Maine Sen. George Mitchell, ex-New Mexico Gov. Bill Richardson and Prince Andrew, Duke of York.
Virginia Roberts Giuffre, who has long claimed Epstein forced her to have sex with powerful men, claimed in the lawsuit that Epstein and his associate, Ghislaine Maxwell, kept her as a "sex slave" in the early 2000s when she was underage.
Giuffre claimed in the unsealed May 2016 deposition to have been trafficked to have sex with and provide erotic massages to powerful politicians, foreign leaders, and well-heeled businessmen.
Her attorney, Brad Edwards, reacted to Epstein's apparent suicide on Saturday, telling Fox News it was "unfortunate and predictable."
"The fact that Jeffrey Epstein was able to commit the selfish act of taking his own life as his world of abuse, exploitation, and corruption unraveled in both unfortunate and predictable," he said in a statement. "While we engaged in contentious legal battles for more than a decade, this is not the ending anyone was looking for."
He continued: "The victims deserved to see Epstein held accountable, and he owed it to everyone he hurt to accept responsibility for all of the pain he caused. It is never too late to come forward with information. We will continue to represent his victims and will not stop in their pursuit of finality and justice."
Epstein's arrest drew national attention, particularly focusing on a deal that allowed Epstein to plead guilty in 2008 to soliciting a minor for prostitution in Florida and avoid more serious federal charges.
Federal prosecutors in New York reopened the probe after investigative reporting by the Miami Herald stirred outrage over that plea bargain.
But his lawyers maintained that the new charges brought by federal prosecutors in New York were covered by the deal and were improper. They said he hasn't had any illicit contact with girls since serving his 13-month sentence in Florida.
High-profile attorney Lisa Bloom, who presents some of Epstein's accusers, tweeted Saturday that his death means a "consciousness of guilt."
"He was charged with only two counts. But he knew. He knew he was guilty, and all of his money would not prevent the inevitable conviction. He knew justice was coming and he could not face it", she wrote.
David Boies, who represents several women allegedly victimized by Epstein, told Fox News: “This is the end of one chapter, but only one chapter, of the battle to bring the sex traffickers to justice. Jeffrey Epstein did not act, and could not have done what he did, alone. Justice demands that those who acted with him also be held to account.”
Before his legal troubles, Epstein led a life of extraordinary luxury that drew powerful people into his orbit.
He socialized with princes and presidents and lived on a 100-acre private island in the Caribbean and one of the biggest mansions in New York. A college dropout, he became a sought-after benefactor of professors and scientists, donating millions of dollars in donations to Harvard University and other causes.
Still, it was never entirely clear how the middle-class Brooklyn math whiz became a Wall Street master of high finance.
Epstein's death is likely to raise questions about how the Bureau of Prisons ensures the welfare of high-profile inmates. In October, Boston gangster James "Whitey" Bulger was killed in a federal prison in West Virginia where had just been transferred.
Fox News' Bryan Llenas, Robert Gearty, Marta Dhanis, Brooke Singman, Travis Fedschun, and the Associated Press contributed to this report.