Rationale: Physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD). COPD has a systemic component that includes significant extrapulmonary effects that may contribute to its severity in individual patients. Objective: To investigate the association of extrapulmonary effects of the disease and its comorbidities with reduced physical activity in patients with COPD. Methods: In a cross-sectional study, 170 outpatients with COPD (GOLD stages I-IV; BODE score 0 - 10) underwent a series of tests. Physical activity was assessed over 5 to 6 consecutive days by using a multisensor accelerometer armband that records steps per day and the physical activity level (total daily energy expenditure divided by whole-night sleeping energy expenditure). Cardiovascular status was assessed by echocardiography, vascular Doppler sonography, and levels of N-terminal pro-B-type natriuretic peptide. Mental status, metabolic/muscular status, systemic inflammation, and anemia were assessed by Beck Depression Inventory, bioelectrical impedance analysis, handgrip strength, high-sensitivity C-reactive protein/fibrinogen, and hemoglobin, respectively. Measurements and Main Results: In a multivariate linear regression analysis using either steps per day or physical activity level as a dependent variable, the extrapulmonary parameters that were associated with reduced physical activity in patients with COPD independently of GOLD stages or BODE score were N-terminal pro-B-type natriuretic peptide levels, echocardiographically measured left ventricular diastolic function, and systemic inflammation. Conclusion: Higher values of systemic inflammation and left cardiac dysfunction are associated with reduced physical activity in patients with COPD.