The musician - who was a founding member of the rock band - "passed peacefully" on Friday morning (25.10.24).
A statement posted on his Instagram page reads: "Phil Lesh, bassist and founding member of The Grateful Dead, passed peacefully this morning.
"He was surrounded by his family and full of love. Phil brought immense joy to everyone around him and leaves behind a legacy of music and love.
"We request that you respect the Lesh family's privacy at this time."
Lesh's cause of death has not been revealed. However, the musician - who played bass guitar in the band for three decades - had a series of different health issues over the years.
He was diagnosed with prostate cancer in 2006 and bladder cancer in 2015, while he also underwent a liver transplant in 1998 due to a hepatitis C infection.
Lesh was inducted into the Rock and Roll Hall of Fame in 1994 alongside other members of the Grateful Dead.
And following the death of lead singer Jerry Garcia in August 1995, he continued to tour with former members of the band and other musicians as the Other Ones, the Dead, and Furthur.
Despite this, Lesh was missing from Dead and Company, the band's most-recent incarnation, which was fronted by John Mayer.
The 'Unbroken Chain' hitmaker actually scaled back his touring commitments over the last decade, and he also made a concerted effort to keep a relatively low profile.
Lesh - who trained as a trumpet player, before switching his attention to the bass - is survived by his wife, Jill, and their two sons, Grahame and Brian.