Having given birth to her youngest child, Margaret, two years previously in July 1560, the Countess of Bedford had returned to court, and resumed her duties within the Royal Household and the queen's Privy Chamber. And it was at Greenwich during this busy summer period that Margaret appears to have contracted the disease which would claim her life: smallpox.

In October 1562, less than three years after her accession to the throne, Elizabeth I contracted the highly-infectious smallpox virus; this led to her becoming critically ill, and subsequently raised questions in regards to the governing of a country with an incapacitated queen, and speculation relating to the future of the English monarchy.

On This Day (27 Aug) in 1562, Margaret St John, Lady Russell, Countess of Bedford, died from smallpox at Woburn Abbey.