The prevalence and parasitemia of Hepatozoon caimani in the natural population of the caiman, Caiman yacare, from the Pantanal area, state of Mato Grosso do Sul, central Brazil, were evaluated according to gender and month of capture from July 2006 to February 2008. Blood samples were obtained bimonthly from a total of 229 caimans, and 76% were positive. Prevalence varied significantly according to sampling month and animal size. Almost all adults (100%) and young-adults (97%) were positive, while 63% of juvenile caimans were positive and all of the youngest individuals were negative. These results indicate that caimans are infected for the first time as juveniles. The mean parasitemia in blood was 13.5 ± 13.0 (n = 174; 1–96 parasites) and did not significantly vary with respect to gender, month of sampling, size, or weight of the caiman. The frequency distribution of parasites in the caiman population was aggregated. Differences in feeding habits and exposure to vectors between the youngest caimans and juveniles are hypothesized as the main risk factors for caimans to acquire H. caimani in central Brazil.