Background: This study investigated the effects of levetiracetam (LEV) treatment on cardiac rhythm and heart rate variability. Methods: The study included two groups of patients diagnosed with non‐lesional epilepsy who had not yet been treated and who presented to the outpatient pediatric neurology clinic at Van Training and Research Hospital, Van, Turkey, between 2019 and 2020. The heart rate variability (HRV) of 47 patients in the first group, before and at the 3rd month of treatment, and intravenous (IV) LEV loading in 13 patients in the second group was evaluated by Holter electrocardiography (ECG). Results: It was determined that the values of triangular index, standard deviation of the RR intervals over a 24‐hour period (SDNN), standard deviation of all 5‐minute mean RR intervals (SDANN), mean of standard deviations of all normal RR intervals (SDNNI), the percentage of RR intervals with >50‐millisecond variation (PNN50), and the square root of mean squared differences of successive RR intervals (RMSSD). HRV of 47 patients under LEV treatment significantly increased in the 3rd month of treatment compared to baseline (p < 0.05). No difference was found in HRV between the intravenous loading and the control group (p > 0.05). Conclusions: Our study suggests that the sympathovagal balance before treatment in the patient group is in favor of the sympathetic nervous system and that the sympathovagal imbalance improves after treatment. Our results show that LEV monotherapy and loading have no negative effect on HRV and potential cardiac arrhythmia risk in children with epilepsy. [ABSTRACT FROM AUTHOR]