Background: The increasing incidence of obesity and its co-morbid situations poses a great challenge to worldwide health. Obesity has numerous co-morbidities including airway illness, insulin resistance, type 2 diabetes, atherosclerosis, peripheral polyneuropathy (PN) and cancer. Endocan is a proteoglycan that could be used as a biomarker of endothelial dysfunction. Aim of Study: The current study aimed to investigate plasma endocan level in non-diabetic obese patients and to explore the association between circulatory endocan with the clinical and electrophysiological tests of PN in obese patients. Methods: This cross-sectional controlled study enrolled 170 obese patients and 100 control group. The obese group was sub-classified according to BMI (Body Mass Index) into three groups; all participants were subjected to a complete neurological examination. The motor nerve conduction study of [median nerve, ulnar nerve, and Common Peroneal Nerve (CPN)] and the sensory nerve conduction study of [median, ulnar and sural nerves] of all subjects were estimated. Blood sampling and biochemical analysis for parameters of metabolic syndrome (MetS) were done, in addition, Doppler evaluation of Carotid Intima Media Thickness (CIMT) using 0.9mm thickness as a cut-off point was used for identification of atherosclerosis. We measured plasma endocan by Enzyme-Linked Immunosorbent Assay (ELISA). Results: Obese patients with PN had statistically significant higher levels of plasma endocan (218.6±26.26) compared to obese patients without PN (135.5±21.6) and controls (13.1± 3.2). Plasma endocan level was positively correlated with Toronto Clinical Scoring System (TCSS) and negatively correlated with measures of electrophysiological tests; Motor Nerve Conduction Velocities (MNCV) of median, ulnar nerves, Sensory Nerve Conduction Velocities (SNCV) of median and ulnar nerves, Compound Muscle Action Potential (CMAP) amplitude of median and ulnar nerves and Sensory Nerve Action Potential (SNAP) amplitude of median, ulnar and sural nerves. The identification of optimum cut-off point of serum Correspondence to: Dr. Nearmeen M. Rashad, E-Mail: nrashad78@yahoo.com, n.rashad@zu.edu.eg.com endocan could help in evaluating non-diabetic obese patients with PN in attempt to decrease health hazards related to neuropathy. Conclusion: Obese patients with PN had higher values of circulating endocan than obese patients without PN; the diagnostic power of circulating endocan was highly significant thus it could be used as a diagnostic biomarker of PN.