Our key findings include 1) significant association of CYP2C19 genotype with plasma PZQ concentrations and its metabolic ratio (trans-4-OH-PZQ/PZQ) and 2) no significant effect of CYP3A4, CYP3A5, CYP2C19, and CYP2C9 genotypes on schistosomiasis treatment efficacy at 3-weeks post-treatment, 3) a borderline significant association of CYP3A5 genotype with treatment-associated adverse events, being higher among carriers of defective variant alleles (*3, *6 and *7). Here, CYP2C19 is linked to schistosomiasis.