She married Otto Thott in 1579, an older man than her: he was 33. She had one child with him before he died on 23 March 1588. Their son was , born in 1580. Upon her husband's death, Sophie Thott managed his property in Eriksholm (today Trolleholm Castle), running the estate to keep it profitable until her son came of age. During this time, she also became a horticulturalist, in addition to her studies in chemistry and medicine. The gardens she created in Eriksholm were said to be exceptional. Sophie was particularly interested in studying chemistry and medicine according to Paracelsus, in which small doses of poison might serve as strong medicines, and used her skills to treat the local poor. She was devoted to the study of astrology and helped her brother with producing horoscopes.