AIM: The aim of the current study was to evaluate the index of Cardiac Electrophysiological Balance (iCEB) in hospitalized COVID-19 patients receiving Hydroxychloroquine / azithromycin (HCQ / AZ) combination therapy to determine the susceptibility to ventricular arrhythmia among these patients. METHOD: Sixty-seven COVID-19 patients admitted to the ward were included in the study. Electrocardiograms (ECGs) were obtained from all patients before the initiation of treatment and on treatment day 5. QT/QRS (iCEB) and QTc/QRS (iCEBc) ratios were calculated. RESULTS: QRS, QT and QTc intervals were significantly prolonged on day 5 measurements compared to pre-treatment period (p <0.05). Overall, mean iCEB was 3.6+/-0.4 before treatment and 3.8+/-0.4 on day 5 in the study population (p <0.001). Considering the iCEBc values, a significant increase was observed in patients receiving HCQ/AZ treatment compared to pre-treatment period (4.1+/-0.5 vs 4.4+/-0.6; p <0.001). CONCLUSIONS: To the best of our knowledge, this was the first study to investigate iCEB and iCEBc parameters in patients with COVID-19 on HCQ/AZ therapy. In this study, we demonstrated significantly increased iCEB and iCEBc values following HCQ/AZ treatment in COVID-19 patients. iCEB and iCEBc may serve as a noninvasive, simple, and novel biomarker for detecting increased pro-arrhythmia risk in COVID-19 patients (Tab. 3, Fig. 3, Ref. 36).