MacDonald suffered in her later years with heart trouble. She worsened in 1963 and underwent an arterial transplant at Methodist Hospital in Houston, Texas. Nelson Eddy, in Australia on a nightclub tour, pleaded illness and returned to the States at word of MacDonald's surgery. After the operation she developed pleurisy and was hospitalized for two-and-a-half months. Her friends kept the news from the press until just before her release. Her large home was sold and she moved into a Los Angeles apartment that would not require so much of her energies. Her husband, Gene Raymond, moved into an adjoining apartment. Nelson Eddy took his own apartment in the opposite building. MacDonald was again stricken in 1964. Nelson Eddy was with her when she was admitted to UCLA Medical Center, where on Christmas Eve she was operated on for abdominal adhesions. She was able to go home for New Year's, but in mid-January husband Raymond flew her back to Houston. It was hoped that pioneer heart surgeon Dr. Michael DeBakey, who had recently operated successfully on the Duke of Windsor, could perform the same miracle for her. She checked in on January 12, and a program of intravenous feedings was begun to build her up for possible surgery. MacDonald died two days later on January 14 at 4:32 pm, with her husband at her bedside. According to press reports, MacDonald's last words to Raymond while he massaged her feet were "I love you." He replied "I love you, too;" she smiled and succumbed.
MacDonald was interred on January 18, 1965 in a crypt at Forest Lawn Memorial Park in Glendale, California which reads Jeanette MacDonald Raymond. Nelson Eddy, who told Jack Paar on The Tonight Show, "I love her [MacDonald]," broke down when interviewed by the press the evening of her death. He survived MacDonald by two years.