Abstract Background Neurophysiological exploration of ICU delirium is limited. Here, we examined EEG characteristics of medical-surgical critically ill patients with new onset altered consciousness state at high risk for ICU delirium. Methods Pre-planned analysis of non-neurological mechanically ventilated medical-surgical ICU subjects, who underwent a prospective multicenter randomized, controlled EEG study (NCT03129438, April 2017-November 2018). EEG characteristics, according to the 2012 ACNS nomenclature, included background activity, rhythmic periodic patterns/epileptic activity, amplitude, frequency, stimulus-induced discharges, triphasic waves, reactivity and NREM sleep. We explored EEG findings in delirious vs. non-delirious patients, specifically focusing on presence of burst-suppression and rhythmic periodic patterns (ictal-interictal continuum), and epileptiform activity (ictal EEG). Results We analyzed 91 patients (median age, 66 years) who underwent EEG because of new onset altered consciousness state at a median 5 days from admission; 42 patients developed delirium (46%). Burst-suppression (10 vs. 0%, p = 0.02), rhythmic/periodic patterns (43% vs. 22%, p = 0.03) and epileptiform activity (7 vs. 0%, p = 0.05) were more frequent in delirious vs. non-delirious patients. The presence of at least one of these abnormal EEG findings (32/91 patients; 35%) was associated with a significant increase in the likelihood of delirium (42 vs. 15%, p = 0.006). Cumulative dose of sedatives and analgesics, as well as all other EEG characteristics, did not differ significantly between the two groups. Conclusion In mechanically ventilated non-neurological critically ill patients with new onset alteration of consciousness, EEG showing burst-suppression and/or ictal-interictal continuum findings indicates a higher risk of ICU delirium, independently of sedation and analgesia.