OBJECTIVES: This study aimed to determine whether patients on extracorporeal membrane oxygenation (ECMO) with coronavirus disease 2019 (COVID-19) achieved lower rates of physical therapy participation and required more sedation than those on ECMO without COVID-19. DESIGN: Retrospective, observational, matched-cohort study. SETTING: Bicenter academic quaternary medical centers. PARTICIPANTS: All adults on ECMO for severe COVID-19-associated acute respiratory distress syndrome (ARDS) during 2020 and matched (matched 1:1 based on age +/- 15 years and medical center) adults on ECMO for ARDS not associated with COVID-19. INTERVENTIONS: Observational only. MEASUREMENTS AND MAIN RESULTS: Measurements were collected retrospectively during the first 20 days of ECMO support and included daily levels of physical therapy activity, number of daily sedation infusions and doses, and level of sedation and agitation (Richmond Agitation and Sedation Score). During the first 20 days of ECMO support, the 22 patients who were on ECMO for COVID-19-associated ARDS achieved a similar proportion of days with active physical therapy participation while on ECMO compared to matched patients on ECMO for non-COVID-19 ARDS (22.5% v 7.5%, respectively; p value 0.43), a similar proportion of days with Richmond Agitation and Sedation Score >/=-2 while on ECMO (47.5% v 27.5%, respectively; p value 0.065), and a similar proportion of days with chemical paralysis while on ECMO (8.4% v 18.0%, respectively; p value 0.35). CONCLUSIONS: The results of this matched cohort study supported that sedation requirements were not dramatically greater and did not significantly limit early physical therapy for patients who had COVID-19-associated ARDS and were on venovenous extracorporeal membrane oxygenation (VV-ECMO) versus those without COVID-19-associated ARDS who were on VV-ECMO.