Background: Sialic acid is a component of serum that is elevated in diseases such as diabetes and certain malignancies. The normal range of SSA concentration and serum neuraminidase activity in different populations are varied, probably due to racial differences. Objective: The purpose of the present study was to obtain the average SSA concentration and serum neuraminidase activity, in an Iranian population, and to show whether these indices could indicate the severity, and serve as risk factors, for diabetes and CVD. Methods: Serum sialic acid (SSA) concentration and neuraminidase activity were measured in 214 male and female patients and 150 normal individuals. The patient groups were composed of diabetics, diabetics with vascular disease and CVD patients. A mean±SEM value of 60.06±3.36 mg/100 ml for SSA and 50.82±2.93 mU/ml for serum neuraminidase activity were obtained in the randomly selected normal controls. Results: SSA was significantly higher in the patient groups as compared to the values in the age and sex-matched controls. Increased SSA in the diabetics with vascular complications was significantly higher than that for diabetics without retinopathy. The serum neuraminidase activity was also increased in the patient groups. In contrast to the pattern for SSA levels, serum neuraminidase activity in the diabetic patients was not significantly lower than that for diabetics with retinopathy. Conclusion: While serum neuraminidase activity may serve as a factor which tends to increase in CVD, diabetic and retinopathic patients, it may not be as reliable as the SSA level which correlates the severity or monitoring of these diseases. However, it can be a useful index to be used along with SSA measurements.