Background In subjects with chronic obstructive pulmonary disease (COPD), symptoms of fatigue, concomitant heart disease and low physical activity levels are more frequently described than in subjects without COPD. However, there are no population-based studies addressing the relationship between physical activity, fatigue and heart disease in COPD. The aim was to compare physical activity levels among subjects with and without COPD in a population based study, and to evaluate if concomitant heart disease and fatigue was associated to physical activity. Methods In this, 470 subjects with COPD and 659 subjects without COPD (non-COPD) participated in examinations including structured interview and spirometry. A ratio of the forced expiratory volume in one second (FEV1)/best of forced vital capacity (FVC) and vital capacity (VC) < 0.7 was used to define COPD. Physical activity was assessed with the International Physical Activity Questionnaire (IPAQ), and fatigue with the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F). Results The prevalence of low physical activity was higher among subjects with FEV1 < 80% predicted compared to non-COPD subjects (22.4% vs. 14.6%, p=0.041). The factors most strongly associated with low physical activity in subjects with COPD were older age, OR 1.52, (95% CI 1.12 – 2.06), a history of heart disease, OR 2.11 (1.10 - 4.08), and clinically significant fatigue, OR 2.33 (1.31 - 4.13); while obesity was the only significant factor among non-COPD subjects, OR 2.26 (1.17 – 4.35). Conclusion Physical activity levels are reduced when lung function is decreased below 80% of predicted, and the factors associated with low physical activity are different among subject with and without COPD. We propose that the presence of fatigue and heart disease are useful to evaluate when identifying subjects for pulmonary rehabilitation.