Hanneman died Thursday morning of liver failure at a Los Angeles hospital with his wife, Kathy, by his side, according to Slayer spokeswoman Heidi Robinson-Fitzgerald. He was 49.
Family members and doctors were not immediately available to discuss the cause of death.
Robinson-Fitzgerald said Hanneman had been slowly recovering from necrotizing fasciitis, a flesh-eating disease that nearly cost him his arm. Such an infection can develop from a minor cut or scratch; Robinson-Fitzgerald blamed the spider bite, for which he failed to seek immediate treatment. She said he was bitten while in a friend's hot tub.
Infections by flesh-eating bacteria are rare. The affliction can destroy muscle, fat and skin and may require surgery to remove the diseased tissue to save a patient's life.
Hanneman had several operations to remove dead and dying tissue from his arm, the band said on its website last year.
It's unknown if Hanneman was bitten by the dangerous brown recluse spider. Robinson-Fitzgerald said the spider that bit the Slayer guitarist was never recovered.
The government estimates roughly 750 flesh-eating bacteria cases occur each year, usually caused by a type of strep germ. About 1 in 5 people with the most common kind of flesh-eating strep bacteria die.
People with weakened immune systems can be more at risk.
Flesh-eating bacteria, by itself, doesn't cause liver failure. But at least one type of strep bacteria can cause streptococcal toxic shock syndrome, which can lead to liver failure.
It is unclear whether an autopsy will be scheduled. No funeral arrangements have been made.
"Jeff Hanneman will always be a metal god," rocker Andrew W.K. posted on Twitter.
Hanneman co-founded the thrash metal pioneers in Huntington Beach, Calif., in 1981.