Background: C-reactive protein (CRP) is often used as clinical marker of acute systemic inflammation. Since low-grade inflammation is evident in chronic diseases like chronic obstructive pulmonary disease (COPD), new methods have been developed to enhance sensitivity of CRP assays in the lower range. We aimed 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 (by high-sensitivity particle-enhanced immunonephelometry), interleukin-6 (IL-6) (by ELISA), body composition (by bio-electrical impedance analysis), resting energy expenditure (REE: by ventilated hood), exercise capacity (6-minute walking distance, maximal and submaximal bicycle ergometry test), health status (by SGRQ) and lung function were determined in 102 clinically stable COPD patients (GOLD stage II-IV). The cut-off point of normal vs. elevated CRP level was 4.21 mg/l. Results: CRP was elevated 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) as well as 6-minute walking distance (p=0.014) were lower. The symptom score of the SGRQ (p=0.003) was lower in patients with elevated CRP as were postbronchodilator FEV1 (p=0.031) and reversibility (p=0.001). Regression analysis also showed that, adjusted for FEV1, age and gender, 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.