In a retrospective postmortem study, we examined the neuronal expression of active caspase-3, a specific apoptotic marker, in the brainstem of 67 infants dying from sudden infant death syndrome (SIDS), and 25 age-matched control infants (non-SIDS). Neuronal immunostaining for active caspase-3 was semi-quantitatively scored in nuclei from five brainstem levels: rostral, mid and caudal pons, and rostral and caudal medulla. Regardless of the cause of death (SIDS vs. non-SIDS), age-related differences in active caspase-3 expression were identified, predominantly in the medulla. No gender-related differences were identified. Comparing SIDS to non-SIDS cases, increased active caspase-3 expression was restricted to four nuclei in the caudal pons (abducens, facial, superior olivary, and pontine nuclei) and two nuclei in the rostral medulla (hypoglossal and dorsal motor nucleus of the vagus). We conclude that neuronal apoptosis is increased in the brainstem of SIDS compared to non-SIDS infants.