Introduction The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a severe respiratory disease with a 3% global mortality. In the absence of effective treatment, controlling of risk factors that predispose to severe disease is essential to reduce coronavirus disease 2019 (COVID-19) mortality. Large observational studies suggest that exercise can reduce the risk of all-cause and disease-specific mortality. The aim of this study was to analyze the influence of the baseline physical activity level on COVID-19 mortality Methods This is a retrospective cohort study that included patients between 18 and 70 years old, diagnosed with COVID-19 and hospitalized in our center between February 15 and April 15, 2020. After discharge all the patients included in the study were contacted by telephone. Baseline physical activity level was estimated using the Rapid Assessment of Physical Activity Scale questionnaire and patients were divided into two groups for comparison: sedentary patients (group 1) and active patients (group 2). Results During the study period 552 patients were admitted to our hospital and met the inclusion criteria. Global mortality in group 1 was significantly higher than in group 2 (13.8% vs 1.8%; p < 0.001). Patients with a sedentary lifestyle had increased COVID-19 mortality independently of other risk factors previously described (hazard ratio 5.91 (1.80-19.41); p = 0.003). Conclusion A baseline sedentary lifestyle increases the mortality of hospitalized patients with COVID-19. This finding may be of great utility in the prevention of severe COVID-19 disease.