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Abstract Background Currently, evidence about the long-term consequences of COVID-19 on return to work and health-related quality of life (HRQoL) is limited. We evaluated return to work and its associations with baseline characteristics and physical and mental recovery over time in patients up to 1 year after hospitalization for COVID-19. Secondly, we aimed to evaluate the association between return to work and health-related quality of life (HRQoL). Methods CO-FLOW, a multicenter prospective cohort study, enrolled adult participants hospitalized for COVID-19, aged ≥ 18 years within 6 months after hospital discharge. Return to work and HRQoL were collected at 3, 6, and 12 months after hospital discharge using the iMTA Productivity Cost Questionnaire and the 36-Item Short Form Health Survey, respectively. Data were collected between July 1, 2020, and September 1, 2022. Generalized estimating equations with repeated measurements were used to assess outcomes over time. Results In the CO-FLOW study, 371 participants were employed pre-hospitalization. At 3, 6, and 12 months post-discharge, 50% (170/342), 29% (92/317), and 15% (44/295) of participants had not returned to work, and 21% (71/342), 21% (65/317), and 16% (48/295) only partially, respectively. ICU admission (adjusted odds ratio (95% confidence interval): 0.17 (0.10 to 0.30), p |