The contribution of intrapartum hypoxia-ischemia to neonatal encephalopathy in the larger preterm infant remains poorly defined. Such infants could become potential candidates for neuroprotective strategies. The objective of this study was to determine in preterm infants of gestation 31 to 36 weeks, with severe fetal acidemia (i.e., cord arterial pH < 7.00) the incidence of moderate to severe neonatal encephalopathy as well as the perinatal characteristics that may facilitate early identification. The data of 61 preterm infants of mean birth weight 1998 gm and mean gestation of 33.6 weeks were retrieved. Short-term abnormal neurologic outcome measures included evidence of encephalopathy with or without seizures or neuroimaging abnormalities. Eight (13%) of 61 infants developed an abnormal neonatal neurologic outcome. More infants with abnormal vs normal outcome had 1-minute Apgar of 0, i.e., 4/8 vs 3/53, 5-minute Apgar score </=5 (7/8 vs 17/53), required chest compressions (5/8 vs 6/53), cord pH (6.75 vs 6.90), and base deficit 20 vs 18 (P < 0.05). By multivariate analysis, only gestation was associated with abnormal outcome (P = 0.0003). We conclude that the larger depressed preterm infant is at increased risk for moderate to severe encephalopathy. Such infants could also be considered potential candidates for neuroprotective strategies.