Louisa May Alcott (1832–1888), famous in her own time and immortalized in ours as a major figure of the "American Renaissance," died at the age of 55 after intermittent suffering over 20 years. Her illnesses evoked intense interest in her time and in ours. Alcott tracked her signs and symptoms (in letters and journal entries), which included headaches and vertigo, rheumatism, musculo-skeletal pain, and skin rashes; in her final years she recorded severe dyspepsia with symptoms of obstruction, and headaches compatible with severe hypertension. Her death came suddenly with a stroke. Standard biographies propose that her illnesses were due to acute mercury poisoning from inorganic mercury medication she received for a bout of typhoid in 1863, a cause she herself believed. We have reviewed Alcott's observations, as well as those of others, and have determined that acute mercury poisoning could not have caused her long-term complaints. We propose instead that Alcott suffered a multi-system disease, possibly originating from effects of mercury on the immune system. A portrait of Alcott raises the possibility that she had systemic lupus erythematosus (SLE).