Adipose tissue secretes adipokines with proinflammatory and anti-inflammatory properties. Our aim was to assess the role of adipose tissue in generalized inflammatory state of advanced NSCLC patients and the possible use of leptin, adiponectin and resistin as diagnostic and prognostic markers. Correlation of adipose tissue with weight loss in advanced NSCLC patients was also studied. Fasting serum levels of leptin, adiponectin and resistin were determined in 101 advanced NSCLC patients (76 without weight loss and 25 with weight loss) and 51 healthy volunteers using commercially available ELISA. Adipokine serum levels were determined at diagnosis, at the end of first-line chemotherapy and at the time of disease progression for those who responded to treatment. Epidemiological, anthropometrical and laboratory data were assessed. Serum leptin and adiponectin levels presented no differences. Serum resistin levels were significantly increased in NSCLC patients after adjustment for age, sex and BMI. Multivariate analysis showed that these adipokines at diagnosis could not be used as predictive factors for overall survival or time to progression. Only serum resistin levels were associated with weight loss. Despite no direct involvement of leptin and adiponectin, resistin as a proinflammatory cytokine may play a role in the pathogenesis of weight loss in NSCLC patients.