Background The birth of an infant requiring admission to a Neonatal Intensive Care Unit (NICU) can represent a considerable source of stress for some parents. Currently, little is known about the factors associated with parental stress response to the NICU, especially for fathers. The objective of this study is to compare sources of NICU stress for mothers and fathers and explore variables associated with NICU stress.Method One hundred and seventy‐two randomly selected couples with an infant admitted to the NICU were administered a structured clinical interview and completed self‐report measures, including the Parental Stress Scale (PSS).Results Mothers had the highest overall stress. The altered parental role was the highest source of stress for both parents. Key general predictors of parental stress were dysfunctional personality traits and high anxiety. For mothers, high stress was associated with lower income, de facto relationship, abnormal pregnancy scan and no previous NICU experience. For fathers, high stress was associated with transfer of the pregnant mother due to complications and early experience of paternal over control.Conclusion Identification of factors that contribute to parent stress can enable health professionals to facilitate parent adaptation and coping, thereby promoting optimal parent–infant relationships and subsequent infant development. Copyright © 2007 John Wiley & Sons, Ltd.