Fluid management in the first postnatal week among infants with perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) is an important knowledge gap. We aimed to evaluate the effects of fluid restriction on short- and long-term outcomes in infants with HIE. Term infants with moderate or severe HIE on therapeutic hypothermia were randomized within 6 hours of age to receive either restricted intravenous maintenance fluids (45 ml/kg/day on day 1 to a maximum of 120 ml/kg/day on day 6) vs conventional fluid (60 ml/kg/day on day 1 to a maximum of 150 ml/kg/day on day 6). The primary outcome was a composite of mortality or neurological abnormality at hospital discharge. We studied neurodevelopmental disability at 18-24 months using Bayley Scales of Infant Development, third edition. A total of 210 infants were randomized. Three infants died during the hospital stay. The primary outcome of mortality or neurological abnormality at discharge was not significantly different between the restricted and the conventional fluid group [57% vs 53%, RR: 1.07 (95% CI: 0.83, 1.37), P-value .58]. The incidence of cranial magnetic resonance imaging abnormalities was similar in the groups (65% vs 71%, P-value .30). There were no differences in the rates of severe neurodevelopmental disability at 18-24 months in the two groups [27% vs 28%, RR: 0.96 (95% CI: 0.62, 1.50), P-value .88]. Adverse outcomes were similar in both groups. Fluid restriction in the first postnatal week of life did not improve short- and long-term neurodevelopmental outcomes in term infants with moderate or severe HIE.