Background: Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated if school-aged children with and without FLG mutations have differences in immune cell numbers. Methods: This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg) and CD27+ and CD27- memory B cells. Sensitivity analysis was performed in 102 AD cases, assessed by parental questionnaires. Results: FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg or memory B cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cells or their subsets. Conclusions: School-aged children with FLG mutations have higher Th22 cell, which might suggest an immunological defense mechanism to an altered skin barrier function. No associations between Th or Treg cells and FLG mutations suggests that FLG mutations do not otherwise affect immune composition in a general pediatric population.