In 1782, Prince Alfred was inoculated against smallpox. The sickness proved too much for the child and in June he was taken to Deal with his governess Lady Charlotte Finch to recover. It was hoped that the sea air, bathing in the water, and horseback riding would improve his condition. While he was there, Alfred endeared himself to many, including an old woman to whom he waved. In spite of his charming disposition, he continued to break out in spots and his chest was troubling him. When he returned to Windsor in August 1782, the doctors inspected him and realized that the boy had only weeks to live. After suffering bouts of fever and continuing problems with his chest, Prince Alfred died on 20 August 1782, at Windsor Castle, Berkshire, not even two years old. Although the household did not go into mourning, his parents took the loss harshly. According to Lady Charlotte Finch, the Queen "cried vastly" and was "very much hurt by her loss and the King also." Later in August 1782 the Queen sent Finch a lock of Alfred's hair stating "Receive This... as an Acknowledgement for Your very affectionate attendance upon my dear little Angel Alfred, and wear the inclosed Hair, not only in remembrance of that dear Object, but also as a mark of esteem from Your Affectionate Queen". Alfred was buried at Westminster Abbey, though his remains were later moved to the Royal Vault in St. George's Chapel, Windsor Castle on 11 February 1820. His father continued to dwell on his death, and the sight of Alfred's posthumous portrait in a family painting by Thomas Gainsborough nearly a year after Alfred's death sent his three eldest sisters into tears. Six months after Alfred's death, his elder brother Octavius succumbed to the smallpox virus, further devastating the king. During one of his bouts of madness in 1812, George would have imaginary conversations with his two youngest sons. His youngest sister Princess Amelia was conceived in the months after Alfred's death, born almost exactly a year after he died. The first of George III and Queen Charlotte's children to die, Alfred died nearly seventy five years before his older sister Mary, who was the last survivor of George III and Queen Charlotte's fifteen children. Alfred is also unique among their first fourteen children for never being an older sibling while he was alive, as the only child younger than him was born after his death.
