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 [β] = −5·86, 95% confidence interval [CI]: −11·11, −0·61, P = 0·029) and memory capacities (β = −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 (β = −1·61, 95% CI: −2·44, −0·77, P < 0·001) than in those with higher values (β = −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.