Isabel's mother Maria Beatrice had twelve pregnancies and gave birth to seven live children, four of whom died in infancy. To her father James, this seemed a repeat of his first marriage to Lady Anne Hyde when six of their eight children died young. Only the last two of Isabel's six siblings survived childhood.
Isabel had six siblings:
Catherine Laura Stuart (1675 – 1676), died at the age of nine months
For most of her short life, Isabel was her parents' only child and was fourth in line to the throne behind her father and her elder half-sisters Mary and Anne from her father's first marriage. She moved down a place in the line of succession when her brother Charles Stuart, Duke of Cambridge was born in 1677. However, he lived for only one month, dying from smallpox. In 1678, Isabel was joined by another sister, Elizabeth, who was also short-lived.
In 1678, the Popish Plot, a fictitious conspiracy alleging that there was a Catholic conspiracy to assassinate Isabel's uncle King Charles II, caused the Duke and Duchess of York, their daughter Isabel and Isabel's elder half-sister Anne to flee for their safety to the Dutch Republic where they stayed with Isabel's elder half-sister Mary and her husband Willem III, Prince of Orange.
However, news of King Charles II being very ill, sent James, Duke of York and his family back to England. Because Charles II and his wife had no children (although Charles had many illegitimate children), his brother James, Duke of York was the heir to the throne. There were fears that Charles II's eldest illegitimate son, James Scott, 1st Duke of Monmouth might usurp the throne if James was not in England when Charles II died. Charles survived and once he was better, he sent the Duke and Duchess of York to Edinburgh for their safety while Anne and Isabel remained in London on Charles II's orders.
Isabel died on March 2, 1681, five months before her fifth birthday, at St. James's Palace in London while her parents were still in Scotland. Her father regretted that he "could not have the satisfaction of seeing and assisting her in her sickness." When he was King James II of England, he named the royal yacht Isabella in her memory. Her mother consoled herself with "thoughts that I have more angels to pray for me." Isabel was buried at Westminster Abbey in the vault of her great-great-grandmother Mary, Queen of Scots on March 4, 1681.
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