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Toxoplasma gondii (T. gondii) infects one-third of the world population, but its association with cognitive functions in school-aged children is unclear. We examined the relationship between Toxoplasma seropositivity and neuropsychological tests scores (including math, reading, visuospatial reasoning and verbal memory) in 1755 school-aged children 12-16 years old who participated to the Third National Health and Nutrition Examination Survey, using multiple linear regressions adjusted for covariates. Toxoplasma seroprevalence was 7.7% and seropositivity to the parasite was associated with lower reading skills (regression coefficient [beta] = -5.86, 95% confidence interval [CI]: -11.11, -0.61, P = 0.029) and memory capacities (beta = -0.86, 95% CI: -1.58, -0.15, P = 0.017). The interaction between T. gondii seropositivity and vitamin E significantly correlated with memory scores. In subgroup analysis, Toxoplasma-associated memory impairment was worse in children with lower serum vitamin E concentrations (beta = -1.61, 95% CI: -2.44, -0.77, P < 0.001) than in those with higher values (beta = -0.12, 95% CI: -1.23, 0.99, P = 0.83). In conclusion, Toxoplasma seropositivity may be associated with reading and memory impairments in school-aged children. Serum vitamin E seems to modify the relationship between the parasitic infection and memory deficiency.