Cryptosporidium, an apicomplexan parasite which infects the small intestine, is a leading cause of diarrheal mortality in children under five. In our cohort of Bangladeshi children, repeated infections occur before immunity develops, typically by age four. Due to the lack of effective treatments for infants, understanding the initial failure of adaptive immune response is crucial for future therapeutic developments. We observed that T follicular helper (Tfh) cells, involved in B cell activation, show an exhaustion-like phenotype in 2-year-old Bangladeshi children – a pattern not observed in American children. In untreated PBMCs, we found a higher percentage of activated (CD40L+) Tfh cells at age 2 compared to age 1 and 3. However, Tfh cells at age 2 fail to increase in activation upon stimulation with PMA/Ionomycin, correlating with peak Cryptosporidium infection rates. Additionally, we found that direct stimulation of Tfh cells in Bangladeshi children’s PBMCs, with Cryptosporidium extract, was only possible in those without repeated infections (p<0.01) and with high anti-Cryptosporidium antibody concentration (p<0.05). By random forest analysis, number of antibiotic treatments (p<0.0001) and time since last antibiotic exposure (p<0.05) were identified as top predictors of Tfh cell dysfunction. Further analysis revealed a dose dependent effect of antibiotic exposure and repeated Cryptosporidium infections (p<0.05). Children with increased antibiotic exposure were 85% more likely to experience reinfection than their unexposed counterparts. These results suggest that antibiotic driven dysfunction of Tfh cells is leading to impaired humoral responses and repeated Cryptosporidium infections.