Background Muscle weakness is exceedingly common in critical illness patients and is well described. However, information on the risk factors of muscle weakness in critically ill patients who received extracorporeal membrane oxygenation (ECMO) support are lacking. Our study aims to clarify the risk factors of ICU-acquired weakness (ICU-AW) in ECMO patients to help early recognize potential weakness. Methods We conducted a retrospective study of critical ill patients who used ECMO during their ICU stay. ICU-AW was diagnosed at the time when patients discharged and had a muscle strength sum score < 48 out of a maximal score of 60. Baseline characters and therapy details were collected from the case report form and inspection report. Results 63 patients receiving ECMO support were divided to ICU-AW group and no ICU-AW group according to the Medical Research Council (MRC) score when discharged. A total of 50 of the 63 patients were diagnosed with ICU-AW. On logistic regression analysis, the use of adrenaline apparently increased the odds of developing ICU-AW (OR=6.8,95%CI 1.19-38.92, p=0.032), and it was independent of all other established risk factors for ICU-AW. Meanwhile, the occurrence of infection during ECMO support significantly increased the risks of ICU-AW (OR=7.3,95% CI 1.28-41.24, p=0.025) and was independently associated with the outcome of ICU-AW. Other factors such as mechanical ventilation duration, steroid use and neuromuscular blockade did not differ significantly between the groups in our analysis. Conclusion Infection during ECMO support and use of adrenaline were found independently associated with the development of ICU-AW.