US Attorney General William Barr says there were "serious irregularities" at the federal prison in New York City where Jeffrey Epstein died.
Barr says the investigation into the disgraced money manager's sex crimes will continue.
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"Any co-conspirators should not rest easy," the top US law enforcement official said during a speech at an event in New Orleans on Monday.
Epstein was found dead on Saturday in an apparent suicide in his cell at the Metropolitan Correctional Centre (MCC) in lower Manhattan, where he was being held on new sex trafficking charges.
He was already a registered sex offender after pleading guilty in 2008 to Florida state charges of unlawfully paying a teenage girl for sex.
Barr announced on Saturday he had asked the Justice Department's inspector general to investigate Epstein's death.
In his remarks on Monday at a national conference of the Grand Lodge Fraternal Order of Police, Barr said the criminal case against Epstein was personally important to him and that the financier's death denied his victims the chance to confront Epstein in a courtroom.
"I was appalled - and indeed the whole department was - and frankly angry to learn of the MCC's failure to adequately secure this prisoner," Barr said.
"We are now learning of serious irregularities at this facility that are deeply concerning and demand a thorough investigation."
Barr did not say what those irregularities were. The decision by officials at the Bureau of Prisons not to keep Epstein on a suicide watch has come under scrutiny.
The prison where Epstein died is run by the federal Bureau of Prisons, a division of the US Justice Department.
Prior to his state conviction for sex crimes, Epstein had counted US President Donald Trump and former president Bill Clinton among his associates.
The New York City medical examiner said an autopsy had been completed on Epstein on Sunday but a determination on the cause of death is still pending.
Epstein was arrested on July 6 and pleaded not guilty to federal charges of sex trafficking involving dozens of underage girls as young as 14, from at least 2002 to 2005.