ObjectiveTo quantify the association between physical activity and risk of SARS-CoV-2 infection, COVID-19-associated hospitalisation, severe illness and death due to COVID-19 in adults.DesignA systematic review and meta-analysis.Data sourcesThree databases were systematically searched through March 2022.Eligibility criteria for selecting studiesPeer-reviewed articles reporting the association between regular physical activity and at least one COVID-19 outcome in adults were included. Risk estimates (ORs, relative risk (RR) ratios or HRs) were extracted and pooled using a random-effects inverse-variance model.ResultsSixteen studies were included (n=1 853 610). Overall, those who engaged in regular physical activity had a lower risk of infection (RR=0.89; 95% CI 0.84 to 0.95; I²=0%), hospitalisation (RR=0.64; 95% CI 0.54 to 0.76; I²=48.01%), severe COVID-19 illness (RR=0.66; 95% CI 0.58 to 0.77; I²=50.93%) and COVID-19-related death (RR=0.57; 95% CI 0.46 to 0.71; I²=26.63%) as compared with their inactive peers. The results indicated a non-linear dose–response relationship between physical activity presented in metabolic equivalent of task (MET)-min per week and severe COVID-19 illness and death (p for non-linearity <0.001) with a flattening of the dose–response curve at around 500 MET-min per week.ConclusionsRegular physical activity seems to be related to a lower likelihood of adverse COVID-19 outcomes. Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19. Given the heterogeneity and risk of publication bias, further studies with standardised methodology and outcome reporting are now needed.PROSPERO registration numberCRD42022313629.