About 10-20% of persons who contract SARS CoV-2 will experience persistent post-acute sequelae of SARSCoV-2 infection (referred here as PASC). Given that persistent symptoms are heterogeneous with multisystem involvement, recent consensus recommendations suggest that a holistic rehabilitation program may be required to manage PASC and restore function. While treatments offered at emerging outpatient COVID recovery clinics are being informed by previous similar diseases, the need is great for a better understanding of the unique needs of this growing population and for tested, efficacious rehabilitation programs to address them. Data from a large and diverse ongoing longitudinal survey of persons positive for COVID-19 at the study health system will serve as the sampling frame from which to enroll PASC study patients. The targeted six-week program will comprise a core set of therapies including individually titrated isometrics, strengthening of accessory breathing muscles and diaphragm, resistance and aerobic conditioning, and neuropsychological and cognitive remediation tailored to patients' needs. Using a randomized controlled trial design, the effectiveness of the supervised multimodal rehabilitation intervention will be compared to that of a self-guided (active control) group receiving patient education materials adapted from the World Health Organization guidelines for PASC management. In addition to walking speed, a widely used global measure of aerobic capacity and endurance, and patient-reported health and functioning (primary outcomes), we will assess intervention effectiveness on: cognitive functioning, pain, fatigue, tension, stress, anxiety, and depression, and self-management of PASC symptoms (secondary outcomes). Outcomes will be measured at 8 weeks and at 90 day's post- study entry to examine sustainability of effects. Recruitment is ongoing. It is unlikely that COVID-19 vaccines will lead to the end of PASC syndrome given the emergence of increasingly infectious variants and the high numbers of individuals with continued symptoms several months from initial infection. High rates of vaccine hesitancy and refusal will also contribute to the persistence of both COVID-19 and PASC. Given the dearth of rigorous scientific evidence regarding effective assessment and treatment of PASC and unresolved questions concerning post-COVID rehabilitation care, the results of this study will have significant implications for both policy and program development. ClinicalTrials.gov ID: NCT06156202.