Mitchell met a school teacher, Frances Tree Tatlock, and they married on 24 January 1832 before sailing for India to continue the missionary work in Bombay. His wife gave birth to a son, Blaney, on 12 November 1832 but he died on 16 August 1833. A second son, Samuel, was born on 5 February 1834. Frances and the children returned to England on board the "Severn" in February 1834, leaving William to continue his missionary work until he returned to England in April 1835 due to his own failing health. After recuperating for some time on the Isle of Wight, Mitchell had a disagreement with his Church Missionary Society employers and started to seek alternative missionary work.