Little is known on the incidence of discomfort during the end-of-life of intensive care unit (ICU) patients and the impact of sedation on such discomfort. The aim of this study was to assess the incidence of discomfort events according to levels of sedation.Post-hoc analysis of an observational prospective multicenter study comparing immediate extubation vs. terminal weaning for end-of-life in ICU patients. Discomforts including gasps, significant bronchial obstruction or high behavioural pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. Level of sedation was assessed using the Richmond Agitation-Sedation Scale (RASS) and deep sedation was considered for a RASS - 5. Psychological disorders in family members were assessed up until 12 months after the death.Among the 450 patients included in the original study, 226 (50%) experienced discomfort after mechanical ventilation withdrawal. Patients with discomfort received lower doses of midazolam and equivalent morphine, and were less likely to have deep sedation than patients without discomfort (59% vs. 79%, p < 0.001). After multivariate logistic regression, extubation (as compared terminal weaning) was the only factor associated with discomfort, whereas deep sedation and administration of vasoactive drugs were two factors independently associated with no discomfort. Long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others.Discomfort was frequent during end-of-life of ICU patients and was mainly associated with extubation and less profound sedation.