Objective: To identify the optimal time for introducing enteral nutrition to critically ill neonates. Methods: This prospective cohort study included all eligible critically ill neonates who were admitted to a multidisciplinary tertiary neonatal intensive care unit (NICU) between 1st June and 30th November 2013. Nutrient intake and clinical outcomes during NICU stay were recorded. The effect of early (＜24 hours after NICU admission) and delayed (≥24 hours) enteral nutrition introduction on clinical outcomes was assessed. Results: Energy deficit in critically ill neonates was frequent: 84.7% could not achieve the caloric goal during the NICU stay. Growth retardation was common especially among the preterm: the frequency of neonates whose weight was below the 10th percentile increased significantly from 21.6% on admission to 67.6% at discharge. Compared with delayed enteral nutrition, early enteral nutrition was associated with better median time to starting weight gain (0 vs 6 days, p=0.0002), a lower chance of receiving parenteral nutrition (41.7% vs 95.9%, p＜0.0001), shorter NICU stays (196 vs 288 hours, p=0.0001), fewer hours on mechanical ventilation and a lower chance of developing pulmonary infection (37.5% vs 56.0%, p=0.005). The accumulated energy deficit to the subjects who were exposed to delayed nutrition could not be compensated by subsequent nutrition. Neonates who underwent mechanical ventilation had suboptimal nutrient delivery: they took longer to gain weight and were more likely to develop respiratory distress and receive parenteral nutrition. Conclusions: Early enteral nutrition initiation (＜24 hours) is recommended. Neonates with mechanical ventilation should be monitored with particular attention.