Detailed knowledge of factors associated with resistance to Schistosoma mansoni infection in endemic areas might facilitate more effective schistosomiasis control. We conducted a cross-sectional study of persons resistant to schistosomiasis and found no association between socioeconomic status and resistance to infection. Mononuclear cells of resistant subjects produced higher levels of interleukin-5 (IL-5), IL-13 and interferon-γ upon stimulation with soluble egg antigen (SEA) compared with infected persons. When stimulated with Sm21.6 or Sm22.6, levels of IL-10 were higher in cell culture of resistant persons. Levels of IgE against soluble adult worm antigen (SWAP) and against interleukin-4-inducing principle from S. mansoni eggs (IPSE) and levels of IgG4 against SWAP, SEA, and Sm22.6 were lower in the resistant group compared with the susceptible group. Our data suggest that socioeconomic status could not fully explain resistance to S. mansoni infection observed in the studied area. However, a mixture of Th1 and Th2 immune responses and low levels of specific IgG4 against parasite antigens could be mediating resistance to infection.