We evaluated the seroprevalence of 10 zoonotic agents among the general population (15 years old and over) of Eastmain and Wemindji, James Bay, Quebec, in 2007. Overall seroprevalence rates were similar between the 2 communities. Nearly half the individuals tested (n = 251; 146 women, 105 men) were seropositive (n = 115) for at least one zoonosis. The highest seroprevalence rates were for Leptospira sp. (23%), Francisella tularensis (17%), and the California serogroup viruses (JC and SSH viruses) (10%). The other zoonoses (Toxoplasma gondii, Coxiella burnetii, Echinococcus granulosus, Toxocara canis, and Trichinella sp.) had seroprevalence rates =5%; no exposures were identified to hantaviruses (Sin Nombre virus). Overall, seropositivity was related to age, gender, hunting, and owning a dog. There was no medical history suggestive of overt diseases. Nonetheless, physicians should consider these agents when confronted with difficult or confusing diagnoses. In particular, the bacterial zoonoses should be ruled out in individuals with high or prolonged fever.