OBJECTIVE: To describe characteristics of a series of patients reporting prolonged symptoms after an infection with coronavirus disease 2019 (COVID-19). PATIENTS AND METHODS: This study describes the multidisciplinary COVID-19 Activity Rehabilitation Program, established at Mayo Clinic to evaluate and treat patients with post-COVID syndrome, and reports the clinical characteristics of the first 100 patients receiving evaluation and management during the timeframe of June 1, 2020, and December 31, 2020. RESULTS: The cohort consisted of 100 patients (mean age, 45.4±14.2 years; 68% women; mean body mass index, 30.2 kg/m2; presenting a mean of 93 days after infection). Common preexisting conditions were respiratory (23%) and mental health, including depression and/or anxiety (34%). Most (75%) had not been hospitalized for COVID-19. Common presenting symptoms ware fatigue (80%), respiratory complaints (59%), and neurological complaints (59%) followed by subjective cognitive impairment, sleep disturbance, and mental health symptoms. More than one-third of patients (34%) reported difficulties in performing basic activities of daily living. Only 1 in 3 patients had returned to unrestricted work duty at the time of the analysis. For most patients, laboratory and imaging tests showed no abnormalities or were nondiagnostic despite debilitating symptoms. Most patients required physical therapy, occupational therapy, or brain rehabilitation. Face-to-face and virtual care delivery modalities were feasible. CONCLUSION: Most of the patients did not have COVID-19-related symptoms that were severe enough to require hospitalization, were younger than 65 years, and were more likely to be female, and most had no preexisting comorbidities before severe acute respiratory syndrome coronavirus 2 infection. Symptoms including mood disorders, fatigue, and perceived cognitive impairment resulted in severe negative impacts on resumption of functional and occupational activities in patients experiencing prolonged effects.