Background: Hyponatremia is classified according to volume status with the help of physical examination, biochemical measures, urine and serum osmolalities, and echocardiography. Bioimpedance spectroscopy (BIS) has been getting popularity for revealing tissue compositions of various patient groups. The aim of this observational study was to investigate the role of BIS for the differential diagnosis of hyponatremia (ClinicalTrials.gov Identifier: NCT01838759). Patients and methods: Personal characteristics of age, sex, weight, height, and blood pressure were recorded. Body composition monitor (BCM) was used for hydration status for each individual. Primary outcome was investigated by the accuracy of volume status measured by BIS. Statistics: Kappa statistic (K) is a measure of agreement between two sources, which is measured on a binary scale (i.e., condition present/absent). K statistic can take values between 0 and 1: poor agreement: K<0.20, fair agreement: 0.2.0-0.3.9, moderate agreement: 0.40-0.59, substantial: 0.60-0.79, very good agreement: 0.80-1.00. Results: Fifty-eight hyponatremia-diagnosed patients, 32 (55.2%) of male with the mean age of 65.2 +/- 11 (40-89) years were included. Kappa statistic (K) were very good (K = 0.925) for male (p<0.00), substantial agreement (K = 0.601) for female (p<0.002) with the use of BIS for the differential diagnosis of either hypo or hypervolemia in hyponatremic patients compared with gold standard tests which were the combination of echocardiography, serum, and urine osmolality biochemical tests, and physical examination. Conclusion: Bioimpedance spectroscopy is a practical and an inexpensive method. This is the first study in the literature showing the role of BIS for the determination of the volume status and differential diagnosis of hyponatremia when compared with echocardiography.