This study examines the stress levels experienced by parents of premature infants in neonatal intensive care units (NICUs) and explores the factors associated with parental stress. A cross-sectional observational design was used, involving 743 parents from nine NICUs in Egypt. The Parent Stress Scale was employed to collect data. The results show that a majority of parents reported high stress in domains such as sight and sound (80.3%), infants' appearance (69%), and the parent-infant relationship (81.4%). About three-quarters (73.6%) of parents experienced high overall stress, with a mean score of 167.56 (21.3). Factors contributing to parental stress included premature infants connected to mechanical ventilators, previous neonatal death, parents living far from hospitals, infants delivered through cesarean section, insufficient income, and prolonged hospitalization beyond 5 days. Mothers were more likely to experience higher levels of stress compared to fathers. Breastfeeding, visiting the baby daily, having living children, and living with a partner were identified as protective factors. The study highlights the significant emotional burden on parents during the neonatal period and suggests interventions to support parents in managing and coping with stress effectively.This study examines the stress levels experienced by parents of premature infants in neonatal intensive care units (NICUs) and explores the factors associated with parental stress. A cross-sectional observational design was used, involving 743 parents from nine NICUs in Egypt. The Parent Stress Scale was employed to collect data. The results show that a majority of parents reported high stress in domains such as sight and sound (80.3%), infants' appearance (69%), and the parent-infant relationship (81.4%). About three-quarters (73.6%) of parents experienced high overall stress, with a mean score of 167.56 (21.3). Factors contributing to parental stress included premature infants connected to mechanical ventilators, previous neonatal death, parents living far from hospitals, infants delivered through cesarean section, insufficient income, and prolonged hospitalization beyond 5 days. Mothers were more likely to experience higher levels of stress compared to fathers. Breastfeeding, visiting the baby daily, having living children, and living with a partner were identified as protective factors. The study highlights the significant emotional burden on parents during the neonatal period and suggests interventions to support parents in managing and coping with stress effectively.