OBJECTIVES: To investigate the prevalence of, and the factors associated with, long-term sick leave in working-age patients diagnosed with COVID-19 in general practices in Germany. METHODS: Patients aged 18-65 years diagnosed with COVID-19 in any of 1255 general practices in Germany between March 2020 and February 2021 were included in the study. Long-term sick leave was defined as sick leave of at least 4 weeks. The association between predefined independent variables and long-term sick leave was studied using an adjusted logistic regression model. RESULTS: This study included 30 950 patients diagnosed with COVID-19 (51.7% women, mean (standard deviation) age 41.5 (+/-13.0) years). The prevalence of long-term sick leave was 5.8%. Female sex, older age, and several conditions (noninfective enteritis and colitis; reaction to severe stress, and adjustment disorders; atopic dermatitis; mononeuropathies; reflux diseases; diabetes mellitus; and hypertension) were positively and significantly associated with long-term sick leave. CONCLUSION: Long-term sick leave was relatively rare in COVID-19 patients followed in general practices in Germany. These results should be confirmed or invalidated in other settings and countries.