The prescription pills went unaccounted for from four of the company's pharmacies in Turlock, Fairfield, Modesto and Dixon, according to the Los Angeles Times.
Authorities suspect thousands of the pills, which include Vicodin and Norco, may have wound up in the hands of dealers and sold on the Black Market.
A special agent from the DEA's San Francisco office says warrants were served to the stores involved last May. The violations carry a maximum fine of $29 million.
CVS is one of the nation's largest retail pharmacy chains.
In 2010, the company was ordered to pay a $75 million fine for its role in selling an ingredient used to make methamphetamine. The feds say the drugstore chain's actions led to a surge in street sales of the illegal drug.
On Tuesday, CVS released the following statement regarding the ongoing investigation: "We are committed to working with the DEA, other regulatory and enforcement agencies, as well as key stakeholders in the medical community, to combat prescription drug abuse and diversion. We are cooperating with the DEA in their review of pharmacy records at a few of our pharmacies in California to determine the reasons for the discrepancies in our record keeping and to correct them. As health care providers, our pharmacists and technicians remain focused on ensuring prescription drugs are only delivered to the patients who need them.
"CVS Caremark takes very seriously the challenge of combating prescription drug abuse and diversion, and we recognize the important role our pharmacists and technicians play on the front lines of solving this problem. As a company, we are investing significantly in internal controls and processes aimed at preventing prescription drug diversion from our pharmacies. For example, we are enhancing internal audit procedures to detect diversion, developing electronic controlled substance ordering and receiving systems, and implementing new storage and control measures for hydrocodone products beyond regulatory requirements across all of our 7,600 stores."
KGO-TV and The Associated Press contributed to this report.