Background: C-reactive protein (CRP) is often used as a clinical marker of acute systemic inflammation. Since low grade inflammation is evident in chronic diseases such as chronic obstructive pulmonary disease ( COPD), new methods have been developed to enhance the sensitivity of CRP assays in the lower range. A study was undertaken to investigate the discriminative value of high sensitivity CRP in COPD with respect to markers of local and systemic impairment, disability, and handicap. Methods: Plasma CRP levels, interleukin 6 (IL-6) levels, body composition, resting energy expenditure (REE), exercise capacity, health status, and lung function were determined in 102 patients with clinically stable COPD ( GOLD stage II - IV). The cut off point for normal versus raised CRP levels was 4.21 mg/l. Results: CRP levels were raised in 48 of 102 patients. In these patients, IL-6 ( p< 0.001) and REE ( adjusted for fat-free mass, p = 0.002) were higher while maximal ( p = 0.040) and submaximal exercise capacity ( p = 0.017) and 6 minute walking distance ( p = 0.014) were lower. The SGRQ symptom score ( p = 0.003) was lower in patients with raised CRP levels, as were post-bronchodilator FEV1 ( p = 0.031) and reversibility ( p = 0.001). Regression analysis also showed that, when adjusted for FEV1, age and sex, CRP was a significant predictor for body mass index ( p = 0.044) and fat mass index ( p = 0.016). Conclusions: High sensitivity CRP is a marker for impaired energy metabolism, functional capacity, and distress due to respiratory symptoms in COPD.