The aim of this study was to examine the inter-relationship between the inflammatory response and resting energy expenditure in patients with non-small cell lung cancer (NSCLC) before and after the onset of weight loss. Healthy subjects (n=7) and patients with NSCLC without weight loss (n=12) were studied. Resting energy expenditure adjusted for metabolically active tissue, as measured by total body potassium, was approximately 15% higher in the NSCLC group (P<0.01). Moreover, the resting energy expenditure, correlated with the magnitude of the inflammatory response (r=0.753, P<0.01). Six cancer patients subsequently lost weight and the relationship between resting energy expenditure and the inflammatory response was maintained. These results highlight the impact of the inflammatory response on the increase in the resting energy expenditure which precedes the onset of weight loss in patients with NSCLC.