Few prior studies have examined the potential health risks from transmission of enteric parasites via aquifers contaminated by wastewater from onsite systems. A cross-sectional study of 600 residents in households served with either onsite wastewater systems and private wells or city sewer/water systems in three different sites in central New Mexico compared serological responses to Cryptosporidium, a common waterborne infections agent. Study participants completed a short self-administered questionnaire with questions on demographic characteristics, characteristics of the onsite wastewater system and private well, and common risk factors associated with cryptosporidiosis. A sample of household tap water was collected, as well as a blood sample from each study participant to measure IgG responses to antigen groups for Cryptosporidium. Logistic regression analysis showed a significant association between having an onsite wastewater system and private well and the 27-kDa marker for Cryptosporidium in the River Valley site after adjusting for covariates (OR = 1.98; 95% CI = 1.11–3.55). This study, together with one prior study, suggests that the presence of onsite wastewater systems and private wells might be associated with an increased risk of Cryptosporidium infection.