Under-nutrition impairs immune responses, but far less is known about the impact of over-nutrition, such as obesity, on the response to vaccines. We measured the effect of childhood overweight status on inflammatory mediators, circulating immunoglobulins and tetanus antibodies in fifteen overweight children (BMI > 85 age-adjusted percentile) and 15 age-matched normal weight controls. Fitness was measured by a progressive ramp type exercise test. Lean body mass (LBM) and fat mass were determined by DXA. Tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1 beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1ra) were used to assess the inflammatory status; and circulating immunoglobulins (IgM, IgA, IgG and IgG subclasses) and specific IgG titer to tetanus were used to assess humoral immunity. Overweight children had higher LBM and percent fat mass, and lower peak VO2 normalized to body weight. IL-6 was significantly higher in the obese children (2.6 +/- 0.3 vs. 1.3 +/- 0.3 pg/ml, in overweight and normal weight children, respectively; p < 0.05). No significant differences were found in TNF-a, IL-1beta and IL-1ra between the groups. No significant differences were found in immunoglobulin levels (IgM, IgA, IgG and IgG subclasses) between the groups. Anti-tetanus IgG antibodies were significantly lower in the overweight children compared to normal weight controls (2.4 +/- 0.6 vs. 4.2 +/- 0.5 IU/ml, in overweight and normal weight children, respectively; p < 0.05). The reduced specific antibody response to tetanus in obese children and adolescent might be due to mechanical factors such as lower relative vaccination dose, or reduced absorption from the injection site due to increased adipose tissue, or related to reduce immune response due to the chronic low grade inflammation expressed by the higher levels of IL-6.