Known as The Big Man for his 6ft 5in frame and seen as The Boss’s right hand man, he was taken to hospital a week ago after falling ill at his home in Singer Island, Florida.
The E Street Band member, who last performed with Springsteen in December last year, reportedly died from complications at a Palm Beach hospital.
Clemons, whose sax was one of the most defining elements of Springsteen’s band, suffered numerous ailments over the last few years. He had double knee surgery and even had to perform from a wheelchair at one point.
But his health seemed to be improving, and just last month the 69-year-old performed with Lady Gaga on American Idol.
Springsteen treated the news “with overwhelming sadness” and paid tribute, saying: “His loss is immeasurable and we are honoured and thankful to have known him and had the opportunity to stand beside him.”
U2 also paid their own tribute while on stage in California, with Bono telling fans: “I want you to think about the beautiful symphonic sound that came out of one man’s saxophone. I want you to think about Bruce Springsteen and the E Street Band.”