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. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )