Objective Although individuals with obesity are susceptible to infection, the underlying causes have not been fully identified. To investigate whether obesity affects immunity, we studied subjects with isolated obesity. Design and subjects Thirty-four obese persons from our outpatient obesity clinic and 50 nonobese healthy control subjects were studied. The effects of weight reduction were evaluated in obese subjects on a very-low-energy diet. We examined blastogenic response, lymphocyte subsets, circulatory TNF-alpha, soluble TNF-alpha receptor 1, soluble TNF-alpha receptor 2, and in vitro TNF-alpha production in obesity. Measurements Lymphocyte subsets were analysed with flowcytometry. TNF-alpha and soluble TNF receptors levels were assayed using commercially available enzyme-linked immunosorbent assay kits. Results Blastogenic responses to phytohemagglutinin or concanavalin A of T cells, CD3(+), CD4(+), CD8(+), CD4(+)CD45RO(+), and TCR alpha beta T cells were significantly diminished in obese subjects. Strong negative correlations were observed between TCR alpha beta and body weight and BMI in obese subjects. Circulatory levels of TNF-alpha, soluble TNF-alpha receptors, and in vitro TNF-alpha production were significantly increased compared to nonobese subjects. In obese subjects, there were significant positive correlations between serum levels of TNF-alpha and waist-hip ratio, serum levels of soluble TNF-alpha receptor 1 and body weight, soluble TNF-alpha receptor 2 and BMI, and soluble TNF-alpha receptor 2 and waist-hip ratio. The T cell responses and previously reduced non-CD8 T cell subsets were increased significantly following weight reduction. Conclusions Our results suggest that subsets of T cell populations and their function may be reduced in human obesity, and that this may be related, at least in part, to the elevated TNF-alpha production. Furthermore, this T cell dysfunction can be recovered by adequate weight reduction.