Preterm birth carries a risk for impaired developmental outcome. We have previously described an association between increased levels of proinflammatory cytokines during the first 72 postnatal hours and cerebral damage as detected by ultrasound in a cohort of 74 very preterm infants. Sixty-seven of 71 surviving children with a mean gestational age of 27.1 (2.0) wk were examined at 2 y corrected age with a standardized neurologic examination and with Bayley Scales of Infant Development. We hypothesized that proinflammatory cytokine concentrations at or shortly after birth would be associated with an adverse developmental outcome. Increased concentrations of TNF-alpha in cord blood odds ratio (95% confidence interval) 3.3 (1.1-10.2), p = 0.013 and at 6 h 7.8 (0.9-71.8), p = 0.015 and of IL-6 in cord blood 1.7 (1.0-2.9), p = 0.048 were associated with psychomotor developmental index <85. Increased concentrations of TNF-alpha in cord blood odds ratio (95% confidence interval) 3.6 (1.002-12.8), p = 0.044 and of IL-8 in cord blood 3.5 (1.2-10.6), p = 0.023 were associated with cerebral palsy. Associations of TNF-alpha and IL-8 in cord blood with the respective outcome measures remained significant after adjustment for other clinical variables. Proinflammation at birth is associated with impaired functional outcome at 2 y of corrected age in children with very preterm birth.