ObjectivesPhysical activity has been proposed as a protective factor for COVID-19 hospitalization. However, the mechanisms underlying this association are unclear. Here, we examined the association between physical activity and COVID-19 hospitalization and whether this relationship was explained by other risk factors for severe COVID-19.MethodWe used data from adults aged 50 years and older from the Survey of Health, Ageing and Retirement in Europe. The outcome was self-reported hospitalization due to COVID-19 measured before August 2020. The main exposure was usual physical activity, self-reported between 2004 and 2017. Data were analyzed using logistic regression models.ResultsAmong the 3139 participants included in the study (69.3 ± 8.5 years, 1763 women), 266 were tested positive for COVID-19 and 66 were hospitalized. Results showed that individuals who engaged in physical activity more than once a week had lower odds of COVID-19 hospitalization than individuals who hardly ever or never engaged in physical activity (odds ratios = 0.41, 95% confidence interval = 0.22–0.74, p = .004). This association between physical activity and COVID-19 hospitalization was explained by muscle strength, but not by other risk factors.ConclusionThese findings suggest that, after 50 years of age, engaging in physical activity more than once a week is associated with lower odds of COVID-19 hospitalization. The protective effect of physical activity on COVID-19 hospitalization is explained by muscle strength.