The influence of acute dietary protein restriction on the development of Babesia microti infection in the mouse model was investigated. Female mice consuming a diet either devoid of protein or adequate with respect to protein were infected with B. microti-parasitized erythrocytes and sacrificed 7 days later. Absence of dietary protein resulted in a delay in the onset of infection and a significantly reduced peak parasitemia. Non-specific antibody responses to heterologous erythrocytes and specific anti-babesial antibody titers were impaired in mice consuming the protein-free diets, suggesting that the enhanced resistance to experimental babesiosis observed in protein-malnourished mice is not an antibody-mediated phenomenon. In addition, protein-malnourished mice did not demonstrate significantly lower concentrations of the serum complement component, C3, which has been implicated as a participant in the invasion process of host erythrocytes by parasites. Serum C3 levels were significantly reduced in infected mice consuming both diets. The mechanism by which acute protein deprivation protects mice against lethal babesiosis remains to be determined.