He died in his last expedition.

One of the interesting facts about Ernest Shackleton is that he died on his last expedition. In December 1919, Shackleton released his own account of the Endurance mission, South, and resumed his lecture tour. 1920 saw Shackleton get weary with the lecture circuit and start to think about doing this last expedition Shackleton described the project as an "oceanographic and sub-Antarctic trip" once the destination moved to Antarctica. The joint venture's objectives are unclear, however, one of them has been cited as circumnavigating the Antarctic continent and looking into various "lost" sub-Antarctic islands, such Tuanaki.

On January 4, 1922, Quest traveled further south and arrived in South Georgia. Shackleton summoned the expedition's physician, Alexander Macklin, to his cabin in the wee hours of the following morning, complaining of back pain and other discomforts. On January 5, 1922, at 2:50 a.m, Shackleton suffered a deadly heart attack.

Shackleton died of a heart attack only four months after the expedition got underway. It is well known that he had health issues while traveling, but he resisted getting help. The cause of death, according to Macklin, who conducted the autopsy, was coronary artery plaque that had been worsened by "overexertion during the debilitation period."