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Illness and death

Henson appeared with Kermit on The Arsenio Hall Show in Los Angeles on May 4, 1990. This was his final television appearance. Shortly afterwards, he privately disclosed to his publicist that he was tired and had a sore throat, but that he believed it would soon go away. On May 12, Henson traveled to Ahoskie, North Carolina, with his daughter Cheryl to visit his father and stepmother. They returned to their home in New York City the following day, and Henson cancelled a Muppet recording session that had been scheduled for May 14, 1990, due to his ill health. His wife came to visit that night.

Henson was having trouble breathing when he woke up at around 2:00 a.m. EDT on May 15, and he began coughing up blood. He suggested to his wife that he might be dying, but he did not want to take time off from his schedule to visit a hospital. Two hours later, Henson agreed to be taken by taxi to the emergency room at New York Presbyterian Hospital in Manhattan. Shortly after admission, he stopped breathing and was rushed into the intensive care unit. X-ray images of his chest revealed multiple abscesses in both of his lungs as a result of a previous Streptococcal pharyngitis (strep throat) bacterial infection he had apparently had for the past few days. Henson was placed on a ventilator but quickly deteriorated over the next several hours despite increasingly aggressive treatment with multiple antibiotics. Although the medicine killed off most of the infection, it had already weakened many of Henson's organs. He died at 1:21 a.m. the following morning, at the age of 53.

Dr. David Gelmont announced that Henson had died from Streptococcus pneumoniae, an infection that causes bacterial pneumonia. However, on May 29, Gelmont reclassified it as organ dysfunction resulting from streptococcal toxic shock syndrome caused by Streptococcus pyogenes. Gelmont noted Henson might have been saved had he gone to the hospital just a few hours sooner. Medical expert Lawrence D. Altman also stated that Henson's death "may have shocked many Americans who believed that bacterial infections no longer could kill with such swiftness." A lack of familiarity with this possibility, combined with the then-recent deaths of prominent men (including Rock Hudson, Liberace, Roy Cohn, and others) whose AIDS deaths had first been publicly euphemized as other illnesses due to AIDS's pervasive stigma, led to a false but widespread rumor that Henson had died of AIDS — a rumor that was swiftly and directly refuted by Dr. Gelmont. Frank Oz believed the stress of negotiating with Disney led to Henson's death, stating in a 2021 interview: "The Disney deal is probably what killed Jim. It made him sick." Henson was cremated and in 1992, his ashes were scattered near Taos, New Mexico.