Epidemiologic data suggest that SIDS is related to the sleep state, but exiguous literature has addressed infants who had been awake at the time of sudden catastrophic deterioration and subsequent death. The aims of this study are to: (1) Report five infants who were awake at the onset of the lethal event, and (2) Discuss potential lethal pathophysiological events that may lead to these circumstances. The demographic and pathologic profiles of these cases are similar to SIDS. Altered responses to severe hypotension, bradycardia, and apnea, perhaps elicited by aspiration and mediated by cerebellar and vestibular structures, might be involved in the pathogenesis of these deaths. Comprehensive medical history review, investigation of the circumstances of death, thorough postmortem examination with ancillary studies, and preservation of tissues for gene testing, are crucial to explaining these deaths. Careful attention should be given to the awake or sleep state immediately prior to the sudden clinical collapse, and death of infants; those who were awake should be reported to enhance understanding of this phenomenon.