It comes after emails appeared to show conversations between the pair about political matters while Lord Mandelson was serving as business secretary and the de-facto deputy prime minister in 2009, in Gordon Brown’s government.
The SNP, Lib Dems and Plaid Cymru had all called for a formal police inquiry, alleging potential misconduct in public office.
Commander Ella Marriott, of the Metropolitan Police, said: “Following the further release of millions of court documents in relation to Jeffrey Epstein by the United States Department of Justice, the Met received a number of reports into alleged misconduct in public office including a referral from the UK Government.
“I can confirm that the Metropolitan Police has now launched an investigation into a 72-year-old man, a former Government Minister, for misconduct in public office offences.
“The Met will continue to assess all relevant information brought to our attention as part of this investigation and won’t be commenting any further at this time.”
Lord Mandelson is set to step down from the House of Lords following the latest revelations.
Documents released by the US Department of Justice on Monday indicate Epstein was sent internal discussions from the heart of the UK government after the global financial crisis.
That includes emails in which Lord Mandelson appeared to tell Epstein he was “trying hard” to change government policy on bankers’ bonuses, and to confirm an imminent bailout package for the euro the day before it was announced.
The peer also appeared to write to Epstein in June 2009 about an “interesting note that’s gone to the PM”, forwarding an assessment by Mr Brown’s adviser Nick Butler of potential policy measures including an “asset sales plan”.
Downing Street earlier said the Cabinet Office had referred how Lord Mandelson handled sensitive government information while he was a minister to the Metropolitan Police.
Mr Brown also said he had written to the force’s commissioner, Mark Rowley, about Lord Mandelson’s contact with Epstein.
The former PM said the alleged leak was “an inexcusable and unpatriotic act at a time when the whole government and country were attempting to address the global financial crisis that was damaging so many livelihoods”.
Lord Mandelson’s representatives have been contacted for comment.
On other claims, Lord Mandelson questioned the authenticity of the documents, citing false claims he had a US social security number, questionable US-dollar cheque payments into UK banks, incorrect beneficiary details, and multiple basic errors in dates, spelling and formatting.
Lord Mandelson is to quit the House of Lords on Wednesday, the Lord Speaker said earlier on Tuesday.
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