Abstract Purpose The objective of this study was to evaluate the use of sedative, analgesic, and neuromuscular blocking agents (NMBAs) in patients undergoing ECMO support. Materials and methods This was a two year, prospective, observational study of adult ICU patients on ECMO support for more than 48 hours. Results We analyzed 32 patients, including 15 VA ECMO and 17 VV ECMO. The median daily dose of benzodiazepines (midazolam equivalents) was 24 mg and the median daily dose of opioids (fentanyl equivalents) was 3875 mcg. There was a moderate negative correlation between the day of ECMO and the median daily benzodiazepine dose (r = −0.5515) and a very weak negative correlation for the median daily opioid dose (r = −0.0053). On average patients were sedated to RASS scores between 0 and −1. Continuous infusions of opioids, benzodiazepines, propofol, dexmedetomidine, and neuromuscular blocking agents were administered on 404 (85.1%), 199 (41.9%), 95 (20%), 32 (6.7%), and 60 (12.6%) ECMO days, respectively. Patients in the VA arm received a continuous infusion opioid (96.4% vs. 81.6% days, P < .001) and benzodiazepine (58.2% vs. 37.0% days, P < .001) more frequently. Conclusions Patients received relatively low doses of sedatives and analgesics while at a light level of sedation on average. Patients rarely required neuromuscular blockade.