Infection with Helicobacter pylori has been proposed to be a common cause of Sudden Infant Death Syndrome (SIDS). We investigated the frequency of H. pylori infection in 160 infant deaths and 156 live controls by means of the Helicobacter pylori stool antigen (HpSA) immunoassay. Histology was performed in 26 randomly selected cases. H. pylori antigen was detected in 8% (12/156) of the live controls compared with 25% (30/122) of SIDS cases (p < 0.001), 53% (9/17) of deaths due to infection (p < 0.001), and 9% (1/11) of accidental/violent deaths (p = 0.60). In the classic age peak for SIDS, 1-5 mo, 31% (21/67) of SIDS cases were HpSA positive compared with 1.5% (1/68) of live controls (p < 0.001). Rod-like immunoperoxidase positive H. pylori organisms were identified in 7/12 HpSA positive gastric antrum sections compared with 2/14 HpSA negative (p = 0.038). Significantly elevated IL-6 levels in cerebrospinal fluid representing signs of central immune stimulation were demonstrated in HpSA positive SIDS victims compared with HpSA negative victims (p = 0.045). Detection of H. pylori antigen in stool is associated with SIDS and deaths due to infections. We hypothesize that H. pylori infection in infancy may be involved as the triggering pathogen for sudden death during the first 5 month after birth.