CNN's calls Saturday to Cale's representatives, the medical examiner's officer in San Diego County and Scripps Memorial Hospital in La Jolla were not immediately returned.
Lynyrd Skynyrd made Cale's song Call Me The Breeze" famous, and bands including Santana, The Allman Brothers, Johnny Cash, and many others covered his songs.
He won a Grammy for his 2006 album with Clapton, called The Road to Escondido.
The singer-songwriter passed away at Scripps Memorial Hospital in La Jolla, his official website said.
There were no immediate plans for funeral services, it said.
His official biography describes Cale as someone for whom music is all he's ever known.