Police found prescription painkillers in Prince’s possession following his sudden death in Minneapolis on April 21, NBC News reported.
Officials have yet to say what role, if any, those drugs may have played.
Last week’s autopsy discounted suicide – but a medical examiner said full results could take several weeks.
Prince Nelson Rogers, 57, was found dead in a lift on his Paisley Park estate.
Sheriff Jim Olson said there was no sign of trauma on Prince’s body, suggesting the singer had died alone.
The DEA will be working to “determine such things as where the medications came from, and what prescriptions Prince had obtained,” NBC reported.
There have been suggestions Prince was addicted to the painkiller Percocet, which he had been taking since 2009 to relieve hip pain.
The singers former percussionist, Sheila E, told the news agency Prince had suffered the effects of years of jumping off speakers on stage while wearing high heels.
However, claims of drug dependency have been refuted by Prince’s long-time lawyer, L Londell McMillan.
Although he admitted that Prince may have taken pills to manage pain, the lawyer said the musician was “not on any drugs that would be any cause for concern”.
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