Our objective was to characterize sedation management in adult patients with severe respiratory distress syndrome (ARDS) treated with venovenous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective chart review of these patients treated at Toronto General Hospital between January 2012 and October 2015. Medications administered (sedative, analgesic, paralytic, and antipsychotic), sedation depth (Sedation Agitation Scale [SAS] score) delirium assessments, and mobilization were recorded daily. Forty-five adults (33 males, median age 47 years; interquartile range [IQR], 35–56]) with ARDS (median PaO2/FiO2 71; IQR 59–83) because of respiratory infection (91%) were treated with VV-ECMO for a median of 11 days (IQR, 7–17). After ECMO initiation, 96% patients were deeply sedated (SAS score < 3) with continuous infusions of midazolam (49%), propofol (18%), or both (29%) and 98% were receiving opioid infusions (93% fentanyl). Patients were deeply sedated for a median of 6 days (IQR, 3–10) after cannulation before transitioning to intermediate or light sedation (SAS score ≥ 3). Before ECMO discontinuation, 77% of surviving patients were intermediately or lightly sedated, 20% were receiving no sedatives, and 9% were receiving no opioids. During ECMO, 58% had positive delirium assessment and 24% experienced agitation (SAS ≥ 6). During ECMO support, 71% received physical therapy that occurred after a median of 7 days (IQR, 4–12) after cannulation. In conclusion, we found that although patients were deeply sedated for a prolonged duration after VV-ECMO initiation, many were able to safely achieve light sedation and active mobilization.