OBJECTIVE Infection with specific pathogens may lead to increased adiposity: a specific adiposity-promoting effect of Ad36 human adenovirus, without the involvement of neurological mechanisms, was reported. The aim of this study is to investigate whether non-diabetic patients with earlier Ad36 infection show greater degrees of overweight obesity, of Insulin Resistance (IR), assessed by homoeostasis-model assessment (HOMA), and/or of other related factors. Moreover, the relationship, if any, among these factors and an earlier Ad36 infection, and the hypothesis of a mechanism involving IR are investigated. METHODS Ad36 seropositivity is assessed in 68 obese and 135 non-obese subjects, along with body composition, HOMA and laboratory investigations. RESULTS Age, body mass index (BMI), waist-hip ratio, blood pressure, insulin, HOMA and triglycerides are significantly greater in the Ad36 seropositive group. Ad36 seropositivity, along with HOMA and total cholesterol, explains BMI variance. No Ad36 seropositivity effect to HOMA could be envisaged by the same statistical model. CONCLUSIONS A significant association of Ad36 seropositivity with obesity and with essential hypertension in human beings is suggested by our study; this association is mostly significant in women. Our results do not support that any Ad36 adipogenic adenovirus effect is operating in human obesity through an insulin-resistance-related mechanism. Ad36 seropositive status could also be a hallmark of a clinical-metabolic profile possibly preceding obesity and diabetes in non-obese patients.