He was 64.
"He was in hospital very near his home in Virginia," his manager
Margo Lewis said.
"He'd been ill for a while and was forced in 2005 to take a hiatus from performing," Ms Lewis said.
Born in Alabama, Pickett moved to Detroit as a teenager and joined the Falcons, a group which also included another future soul star Eddie Floyd, singing on their 1962 gospel-inspired R and B hit I Found a Love.
By 1965, he had signed a solo deal with Atlantic, scoring a chart hit with In the Midnight Hour, which he co-wrote and cut at the famed Stax studio in Memphis.
That success launched a string of raucous hits by Pickett, whose gleeful swagger and raw sexuality earned him the nickname The Wicked Pickett.
Among the soul classics he recorded at the time were Mustang Sally, Funky Broadway and his biggest hit of all, Land of 1,000 Dances which reached number six on the pop charts.
Pickett's last big hit was Fire and Water in 1972, after which his career went into something of a slump although he continued to perform to enthusiastic audiences.
A revival of sorts followed the release of the hugely popular 1991 movie The Commitments, which followed the fortunes of a budding soul band in Dublin, Ireland, and featured several of Pickett's hits as well as a sub-plot in which the band's manager sought to arrange a performance with the soul veteran.
"He was always in demand," Ms Lewis said. "He last performed at the end of 2004."
Pickett was inducted into the Rock and Roll hall of Fame in 1991. His last studio album, It's Harder Now, was released in 1999 to favourable reviews. He is survived by four children.