BackgroundRehabilitation plays a crucial role in restoring work ability and facilitating the reintegration of post-COVID patients into the workforce. The impact of rehabilitation on work ability and return to work (RTW) of post-COVID patients remains poorly understood. This study was conducted to assess the work ability and RTW of post-COVID patients before rehabilitation and 12 months after rehabilitation and to identify physical and neuropsychological health factors influencing RTW 12 months after rehabilitation.MethodsThis longitudinal observational study included 114 post-COVID patients with work-related SARS-CoV-2 infection who underwent inpatient post-COVID rehabilitation with indicative focus on pulmonology and/or psychotraumatology (interval between date of SARS-CoV-2 infection and start of rehabilitation: M = 412.90 days). Employment status, work ability, and the subjective prognosis of employment (SPE) scale were assessed before rehabilitation (T1) and 12 months after rehabilitation (T4). The predictors analysed at T4 were functional exercise capacity, physical activity, subjective physical and mental health status, fatigue, depression, and cognitive function. Longitudinal analyses were performed via the Wilcoxon signed-rank test. Logistic and linear regression analyses identified predictors of work ability and return to work (RTW), whereas mediation analyses examined the relationships between these predictors and work ability.ResultsAt T4, the median of WAI total score indicated poor work ability, which significantly worsened over time (p < 0.001; r = 0.484). The SPE scale significantly increased from T1 to T4 (p = 0.022, r = -0.216). A total of 48.6% of patients had returned to work 12 months after rehabilitation. Fatigue was identified as the main predictor of reduced work ability and RTW, with each unit increase in fatigue severity decreasing the odds of RTW by 3.1%. In addition, physical capacity and subjective health status were significant predictors of perceived work ability.ConclusionsThe findings highlight the significant challenges that post-COVID patients face in regaining work ability and achieving successful RTW 12 months after rehabilitation. Fatigue appears to be an important predictor of work ability and RTW. To optimize recovery and enhance both biopsychosocial health and work ability, it is crucial to develop and implement personalised interventions that address fatigue, improve physical capacity, and support mental health.Trial registrationThis study is registered in the German Clinical Trials Register under DRKS00022928.