OBJECTIVE: Epilepsy is one of the most prevalent neurological conditions and carbamazepine is a commonly used anti-seizure drug (ASD), especially in developing nations. There are reports of carbamazepine causing atrioventricular conduction defects and autonomic dysfunctions and its implication in Sudden Unexpected Death in Epilepsy (SUDEP) is controversial. We planned this study to assess the effect of carbamazepine (CBZ) on autonomic function compared to other ASDs in persons with epilepsy. METHODS: In this cross-sectional study, we assessed the sympathetic and parasympathetic autonomic functions in persons with epilepsy (PWE) on CBZ versus other anti-seizure monotherapy using tests of heart rate variability including its time-, frequency- and non-linear domains, heart rate response to deep breathing, valsalva maneuver, and blood pressure response to isometric handgrip. RESULTS: Persons with epilepsy on CBZ monotherapy did not show a significant reduction in the time domain parameter SDRR compared to other ASDs used as monotherapy (mean鈥?/-鈥疭D, 38.04鈥?/-鈥?8.75鈥痬s vs 44.37鈥?/-鈥?0.35鈥痬s; p鈥?鈥?.125). However, PWE on CBZ had significantly lower time-domain measurements including RMSSD (mean鈥?/-鈥疭D 31.95鈥?/-鈥?7.29鈥痬s vs 42.02鈥?/-鈥?2.29鈥痬s; p鈥?鈥?.018), SDSD (mean鈥?/-鈥疭D 31.91鈥?/-鈥?7.26鈥痬s vs 41.96鈥?/-鈥?2.27鈥痬s; p 0.018), and pNN50 [median (IQR) 05.45(0.69-25.37) vs 16.38(2.32-36.83); p鈥?鈥?.030]. Frequency domain measures of HRV, heart rate responses to deep breathing, valsalva maneuver and tilt-testing and BP responses to valsalva and tilt-testing were not significantly different between the groups. CONCLUSION: The findings of our study indicate reduced parasympathetic activity in persons on CBZ monotherapy compared to other ASDs, which may pose risk of SUDEP. Carbamazepine may thus be avoided in those at risk of autonomic dysfunction and SUDEP.