The number of obese individuals is surging in developed and developing countries. Obesity predisposes to many serious illnesses. Peripheral neuropathy (PN) is one of its major complications. Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by the adipose tissue and is believed to play a principal role in obesity complications. Meanwhile, hs-CRP is a known inflammatory biomarker. This study was designed to detect the role of serum IL-6 and hs-CRP as inflammatory biomarkers in early diagnosis of peripheral neuropathy (PN) in non-diabetic obese patients. Additionally, we aimed to explore the association between IL-6 with the clinical and electrophysiological tests of PN. This cross-sectional controlled study enrolled 150 obese patients and 50 subjects as a control group. The obese groups were subclassified according to BMI into three groups; all participants were subjected to a complete neurological examination and motor, and sensory peripheral nerve conduction studies. Serum IL-6 and hs-CRP levels were assessed using a commercially available ELISA. Our results revealed that obese patients with PN had statistically significant higher values of IL-6 and hs-CRP compared to obese patients without PN and controls (P < 0.001). Meanwhile, levels of both marker were inversely related to nerve conduction velocities (P < 0.001). Obese patients with PN had higher values of serum IL-6 and hs-CRP than diabetic patients without DPN. Because the diagnostic power of both markers in serum was significant, we conclude that they could be a useful diagnostic biomarker of PN.