This study aimed to evaluate the correlation between serum levels of fetuin-A and the presence and severity of erectile dysfunction (ED) in Egyptian population. The study was performed on 60 ED patients and 20 age—matched healthy controls. A comprehensive medical history and complete physical examination were obtained and performed in all participants. ED and its severity were assessed via International Index of Erectile Function (IIEF-5). Doppler ultrasound, fasting blood glucose level, complete lipid profile, serum total testosterone (TT) and serum fetuin-A were performed. Our results revealed that there were no statistically significant differences between the ED group and the controls regarding body mass index, fetal bovine serum, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG). However, IIEF-5 and serum TT levels were significantly lower in ED patients than controls. Regarding serum fetuin-A, our data demonstrated that ED patients had significantly lower serum fetuin-A levels than controls. In addition, patients with severe ED had lower fetuin-A levels than moderate and mild ED (P<0.001). Serum fetuin-A levels are positively correlated with cholesterol, LDL, TG and IIEF-5 and negatively correlated with HDL. In conclusion, serum fetuin-A level could be a potentially useful and sensitive biomarker for ED diagnosis.