The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in China in December 2019 has become a global public health emergency and has had a major impact on physical activity behaviors globally. The resulting COVID-19 pandemic has produced major lifestyle changes for both the general and special populations. Health authorities around the world have been implementing preventive health measures including quarantine and self-isolation to contain the COVID-19 outbreak. During the lockdown period, physical activity is one of the reasons for going outside one’s own home. Indeed, physical activity plays an important role in reducing sedentary lifestyles in general and specific populations including healthy children, adolescents, adults, elderly, athletes, and individuals with Down syndrome. This chapter describes the impact of the COVID-19 pandemic on sedentary behavior and physical inactivity in general and special populations mentioned before. This chapter also demonstrates the importance of physical activity to reduce the harmful effects of the COVID-19 pandemic and provides recommendations on home-based exercise for people to maintain their well-being, level of independence, and physical and mental health.