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Few accurate data are available on the outcome of septic shock in the neonatal period. The objective was to describe outcome and to determine variables associated with death or adverse outcome in neonates with septic shock.Retrospective cohort study.A tertiary neonatal intensive care unit in a university hospital.All patients admitted to the neonatal intensive care unit over a 6-yr period meeting the following criteria: hypotension and/or need for intravenous fluid administration or vasoactive drugs, in the presence of proven or highly probable infection.None.Main outcomes were 28-day mortality and adverse outcome at 18 months of corrected age, defined as death or severe sequelae (cerebral palsy, severe developmental delay, hearing impairment, blindness, or short bowel syndrome). Forty-eight infants were included. Follow-up data at 18 months were obtained for 46 of 48 infants. The 28-day mortality was 40% (19 deaths). Adverse outcome at 18 months of corrected age was observed in 24 of 46 infants (52%; death = 19, severe sequelae = 5). Twenty-eight percent of the infants were alive and had a normal examination at 18 months. Infants with adverse outcome had significantly lower gestational age, birth weight, Apgar score, weight at onset of sepsis, and pH and more often had Gram-negative infection, fetal growth restriction, hypoglycemia, and thrombocytopenia. Significant predictors (multivariate analysis) of 28-day mortality and of adverse outcome at 18 months of corrected age were weight (kg) at the onset of sepsis (odds ratio 0.14, 95% confidence interval 0.03–0.55; odds ratio 0.21, 95% confidence interval 0.06–0.74, respectively) and Gram-negative infection (odds ratio 10.1, 95% confidence interval 1.5–65.7; odds ratio 45.5, 95% confidence interval 3–637, respectively).Septic shock in the neonatal period has a very poor outcome. Data underscore the extreme vulnerability of very low birth weight infants to septic shock, particularly to Gram-negative species.