Muscle dysfunction is one of the most studied systemic effects in patients with chronic obstructive pulmonary disease (COPD) and a predictor of mortality. It can be caused by sedentary habit due to muscle underuse. Conversely, muscle dysfunction also contributes to inactivity in COPD. To date, the underlying mechanisms of muscle dysfunction and their impacts on physical activity (PA) levels in COPD were not explored in a literature review. The aims of this review are to summarise and discuss the link between muscle dysfunction and biology with reduced levels of daily PA in patients with COPD. This manuscript covers the many aspects of physical inactivity in COPD, the relationship between muscle dysfunction and muscle biology with physical inactivity in this population, as well as the strategies used to tackle muscle impairment with a possible positive impact on activity levels in COPD and other complementary strategies to increase PA in this population. (BRN Rev. 2019;5(3):215-29) Corresponding author: Roberto A Rabinovich, Roberto.Rabinovich@ed.ac.uk Key words: Chronic obstructive pulmonary disease. Muscle biology. Muscle dysfunction. Physical activity. BARCELONA RESPIRATORY NETWORK Collaborative research 216 BRN Rev. 2019;5(3) BARCELONA RESPIRATORY NETWORK Collaborative research 217 L. Cruz Mantoani, et al.: Physical Activity and Muscle biology in chronic Obstructive Pumonary Disease BARCELONA RESPIRATORY NETWORK Collaborative research 218 BRN Rev. 2019;5(3) capacity) 36 , capillarisation defects 37 , and altered mitochondrial function 38,39 .