Introduction: Despite the experimental evidence available on the modulating effects of the H1 receptors on the autonomic function, limited research has been done the effects of such receptors through measuring the heart rate variability (HRV) indexes in human. The present study aims to assess the effect of the acute administration of different doses of hydroxyzine on the time and frequency domain of HRV indexes. Methods: Four experiment sessions were held for the fifteen healthy participants. In each session, after the 5-minute baseline electrocardiogram (ECG) recording, one of the four interventions (the intake of a 5, 10 or 20mg hydroxyzine or a placebo) was performed and then the 5-minute ECG recordings were repeated at 30, 60, 90, 120, 180 and 240 minutes after the oral administration. Results: The statistical analysis has shown that at minute 30, hydroxyzine has an inhibitory effect on the sympathetic index low frequency (LFnu), which is eliminated at minute 180. Moreover, from minute 60, hydroxyzine increases vagal HRV indexes, which are then eliminated at minute 240. Conclusion: The findings of the present study showed that histamines, mediated by H1 receptors, have a modulating effect on the cardiac autonomic; however, this modulating effect is then neutralized or eliminated in a short time probably by other cardiac regulatory mechanisms.