Diarrhea is a leading contributor to childhood morbidity and mortality in sub-Saharan Africa. Given the challenge of blinding most water, sanitation, and hygiene (WASH) interventions, diarrheal disease outcome measures in WASH intervention trials are subject to potential bias and misclassification. Using the platform of a cluster-randomized controlled trial of a household-based drinking water filter in western province, Rwanda, we assessed the impact of the drinking water filter on enteric seroconversion in young children as a health outcome and examined the association between serologic responses and caregiver-reported diarrhea. Among the 2,179 children enrolled in the trial, 189 children 6-12 months of age were enrolled in a nested serology study. These children had their blood drawn at baseline and 6-12 months after the intervention was distributed. Multiplex serologic assays for Giardia, Cryptosporidium, Entamoeba histolytica, norovirus, Campylobacter, enterotoxigenic Escherichia coli and Vibrio cholerae were performed. Despite imperfect uptake, receipt of the water filter was associated with a significant decrease in seroprevalence of IgG directed against Cryptosporidium parvum Cp17 and Cp23 (relative risk [RR]: 0.62, 95% confidence interval [CI]: 0.44-0.89). Serologic responses were positively associated with reported diarrhea in the previous 7 days for both Giardia intestinalis (RR: 1.94, 95% CI: 1.04-3.63) and C. parvum (RR: 2.21, 95% CI: 1.09-4.50). Serologic responses for all antigens generally increased in the follow-up round, rising sharply after 12 months of age. The water filter is associated with reduced serologic responses against C. parvum, a proxy for exposure and infection; therefore, serologic responses against protozoa may be a suitable health outcome measure for WASH trials among children with diarrhea.