A prompt and regulated interferon (IFN) system is critical for host defense against infectious pathogens. Although increased susceptibility to infection has been observed in subjects with diabetes or obesity, little is known about the relationship between metabolic disorders and increased susceptibility to infection. In order to evaluate the association between immune function and metabolic parameters, we examined the relationship between capacity of IFN-alpha production and metabolic parameters including fasting plasma glucose (FPG), lipids, uric acid, body mass index (BMI), and blood pressure in 575 healthy subjects. Linear regression analysis showed that log(IFN-alpha production) was positively correlated with log(triglyceride) (r = 0.088, P = 0.03) and uric acid (r = 0.091, P = 0.03), and negatively correlated with age (r = -0.158, P = 0.0001) and FPG (r = -0.088, P = 0.03). Multiple regression analysis showed that log(IFN-alpha production) was independently determined by age (beta = -0.148, P < 0.0001), sex (beta = -0.240, P = 0.0003), and FPG (beta = -0.096, P = 0.0209), suggesting that lesser degrees of hyperglycemia also affect IFN-alpha production. We conclude that hyperglycemia but not BMI, hypertension, or hyperlipidemia may be associated with decreased capacity of IFN-alpha production and glycemic control is critical even for both subjects without any medication for diabetes and subjects under the diagnosis of diabetes on infectious diseases.