Named team president on July 17, 2013, Dee spent 10 years total with San Diego over two stays. During his tenure as CEO, the Padres hired current general manager A.J. Preller and manager Andy Green.
It is unclear who will succeed Dee, but Fowler told the San Diego Union-Tribune that "the search will begin immediately."
In 2014, Dee and the Padres dismissed GM Josh Byrnes, before ultimately naming Preller his successor that summer. Preller is currently serving a 30-day suspension for undisclosed medical information in the Padres' trade of Drew Pomeranz to the Red Sox in July.
Bud Black was dismissed as manager a year after Preller was hired. Green was given the reins last October.
Dee previously worked for the Padres from 1995-2002, beginning as director of corporate development before being promoted to executive vice president of business affairs.
In between his two stints with the Padres, Dee worked for the Red Sox from 2002-09, where he was chief operating officer beginning in 2004. He then spent parts of five years as president and CEO of the NFL's Miami Dolphins, before making a return to San Diego.
AJ Cassavell covers the Padres for MLB.com. Follow him on Twitter @ajcassavell. This story was not subject to the approval of Major League Baseball or its clubs.