Objectives Many patients, due to a combination of illness and sedatives, spend a considerable amount of time in a comatose state that can include time in burst suppression. We sought to determine if burst suppression measured by processed electroencephalography (pEEG) during coma in sedative-exposed patients is a predictor of post-coma delirium during critical illness. Design Observational convenience sample cohort Setting Medical and surgical ICUs in a tertiary care medical center Patients Cohort of 124 mechanically ventilated ICU patients Measurements and Main Results Depth of sedation was monitored twice daily using the Richmond Agitation-Sedation Scale and continuously monitored by pEEG. When non-comatose, patients were assessed for delirium twice daily using Confusion Assessment Method for the ICU (CAM-ICU). Multiple logistic regression and Cox proportional hazards regression were used to assess associations between time in burst suppression and both incidence and time to resolution of delirium, respectively, adjusting for time in deep sedation and a principal component score consisting of APACHE II score and cumulative doses of sedatives while comatose. Of the 124 patients enrolled and monitored, 55 patients either never had coma or never emerged from coma yielding 69 patients for whom we performed these analyses; 42 of these 69 (61%) had post-coma delirium. Most patients had burst-suppression during coma, though often short-lived [ median (intraquartile range) time in burst suppression, 6.4 (1-58) minutes]. After adjusting for covariates, even this short time in burst suppression independently predicted a higher incidence of post-coma delirium [odds ratio 4.16; 95% confidence interval (CI) 1.27-13.62; p=0.02] and a lower likelihood (delayed) resolution of delirium (hazard ratio 0.78; 95% CI 0.53-0.98; p=0.04). Conclusions Time in burst suppression during coma, as measured by processed EEG, was an independent predictor of incidence and time to resolution of post-coma/post-deep sedation delirium. These findings of this single center investigation support lighter sedation strategies.