Reed had been suffering from liver failure and received a transplant earlier this year in June. His literary agent, Andrew Wylie, said the musician passed away on Sunday morning in Southampton, New York, from an illness related to the transplant.
Reed shared a home in Southampton with his wife and fellow musician, Laurie Anderson, whom he married in 2008. Earlier this year, Anderson commented on the transplant: "It’s as serious as it gets. He was dying. You don’t get it for fun."
A few weeks after his surgery, Reed had written on his website: "I am a triumph of modern medicine, physics and chemistry. I am bigger and stronger than ever. My chen tai chi and health regimen has served me well all of these years... I look forward to being on stage performing, and writing more songs to connect with your hearts and spirits and the universe well into the future." His last release was 2011's Lulu, a collaboration with Metallica.
On Twitter, Iggy Pop called the news "devastating", while Kim Gordon of Sonic Youth called it a "massive shock". John Cale, co-founder of Velvet Underground and producer, said on Facebook: "The world has lost a fine songwriter and poet… I’ve lost my school-yard buddy".
Reed's final missive, on his Facebook page, is of a poster of the musician on a stage entrance, simply captioned "The Door". Fans and colleagues such as Howie Klein, who worked with him at Reprise Records, have posted their condolences and memories underneath the image.
"One of the greatest men I ever met and one of the kindest and most loving – and that's from someone who worked with him and knew him since the 1960s," Klein writes.
This image of Reed, taken from his 1959 high school yearbook, has been doing the rounds on Twitter – with a final, now-bittersweet send-off. Goodbye, Lou: