The federal drug enforcement agency is looking into records pertaining to the distribution of prescription drugs handed out to players by trainers and doctors, the source added.
Those records would include documented visits and examinations by doctors, diagnoses and authorized prescriptions written for players. The investigation is described as being in its "early stages."
The DEA would not respond Monday to inquiries specifically on the NFL.
Agency spokeswoman Erin Mulvey in New York told CNN, "We cannot confirm or deny the existence of any investigation."
Depending on what is found, the case could become a civil and/or criminal case with doctors potentially going to jail if convicted of drug-related offenses.
In part, the investigation was prompted by a class-action lawsuit filed in May, 2013 in federal court by nine named retired NFL players representing 1,300 others who claim the NFL "intentionally, recklessly, and negligently created and maintained a culture of drug misuse, substituting players' health for profit," according to court documents.
The players' suit accuses NFL trainers of handing out pills without prescriptions and without regard to possible dangerous interactions with other drugs.
The named players in the lawsuit include former Chicago Bears quarterback Jim McMahon who, according to the lawsuit, says he got hooked on painkillers taking as many as 100 Percocet pills a month.
"Our more than 1300 clients welcome any government investigation which aims to protect them from further harm," Steve Silverman, attorney for the plaintiffs suing the NFL, said in a statement to CNN.
NFL Senior Vice President of Communications Greg Aiello said in a statement Monday that "we are unaware of any such investigation."
It's unclear at this point whether subpoenas have been prepared during this phase of the investigation.
The story was originally reported by the New York Daily News.
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