Homeless people in the United States may experience poor hygiene and spend extended periods of time outdoors, which increases exposure to animal and insect vectors of disease. Despite these risks, efforts to understand frequency and risk factors for zoonotic and vector-borne infections among homeless people have been limited. We queried homeless people in Boston, Massachusetts (n=194) to evaluate exposure to urban wildlife and ectoparasites associated with infection. Thirty percent of participants reported seeing rodents daily, and 25% reported daily sightings of cats. Body lice and fleas were reported by 4% and 11% of participants, respectively. Sleeping outdoors and heavy drinking were positively associated with rodent and ectoparasite exposure. Frequent sightings of rodents and rodent feces among homeless people in particular areas may indicate human exposure risk to urban rodent-borne pathogens, including Leptospira spp, Seoul hantavirus, and Rickettsia akari. Epidemiologic studies of zoonotic and vector-borne infections in this population are warranted.