Divalproex (DVP) is increasingly prescribed to children and adolescents in psychiatric practices. Among the hematologic adverse effects of DVP, decreased platelet count is well described in the medical literature. However, to date, few studies describe the occurrence of macrocytosis as an adverse effect of divalproex. We report two cases of pediatric patients who developed macrocytosis and decreasing platelet counts secondary to DVP treatment. Because macrocytosis remained an asymptomatic nonprogressive condition for our patients, we support the recommendation for closer surveillance of the patients' complete blood counts for development of anemia in addition to thrombocytopenia.