Background: Levetiracetam, a widely used antiepileptic drug in children, has been associated with psychosocial and behavioral problems, which are also influenced by epilepsy variables, including duration or seizure frequency. Purpose: The objective of this study is to investigate the frequency and timing of treatment-emergent psychosocial and behavioral problems in children receiving levetiracetam, irrespective of seizure variables which are possible confounders. Methods: A prospective, case-control study with a 3-month follow-up was conducted. Consecutive children aged 6 to 16years with new-onset partial seizures were included in case of starting treatment with either levetiracetam or valproic acid. Psychosocial and behavioral functioning were assessed using a set of standardized questionnaires including Strengths and Difficulties Questionnaire (SDQ) and Children’s Depression Inventory (CDI) at baseline, 1 and 3-month follow-up. Patients’ baseline scores were compared to healthy subjects. The difference in the follow-up SDQ and CDI scores was evaluated in patients receiving levetiracetam and valproic acid. Results: A total of 101 participants were analyzed; 32 patients in levetiracetam group, 19 patients in valproic acid group and 50 healthy controls. Baseline SDQ and CDI scores were not statistically different between patients and healthy subjects (p > 0.05). No statistically significant difference was observed in CDI, total and subscale SDQ scores between patients receiving levetiracetam or valproic acid during the study period (p >0.05). A girl aged 15years receiving levetiracetam had a CDI score of 18 without suicidal ideation at baseline. She developed suicidal ideation and depression, which resolved after switching of levetiracetam to valproic acid, at the 1-month follow-up. No other psychiatric or behavioral side-effects were observed in other patients. Conclusion: Psychosocial and behavioral side-effects of levetiracetam treatment are not frequent and they don’t emerge in most of children at lower doses. At this dose, and after 3months, using these specific instruments, we did not observe any difference between the valproic acid and levetiracetam treatment groups.