Leptospirosis has been rarely reported in the United States and has been historically related to occupational exposure to infected animals, and contaminated environments. Over the past decade, there are indications that at-risk populations may be changing in the United States, to also include participants in freshwater sports and occasionally individuals living in economically disadvantaged urban inner- city environments. We present a case of Weil`s disease in a 39-year-old homeless man who had been released from prison two weeks prior and denied direct contact with infected animals or contaminated fresh water. Prison inmates and homeless patients are potentially at high risk of rat exposure and infection with Leptospira. A high index of suspicion is needed for diagnosis of leptospirosis in the absence of traditional risk factors. To our knowledge, this is the first case of leptospirosis associated with homelessness and incarceration in the United States. A literature review on leptospirosis cases in Florida over the past 60 years was performed.