Background: The American Academy of Pediatrics and the National Association of Neonatal Nurses recommend that palliative care be provided as standard care in neonatal intensive care units (NICUs). Objectives: The present study aimed to explain the nurses' experiences of barriers to palliative care in NICUs. Methods: This qualitative study was conducted using the content analysis approach in NICUs of Beheshti and Amin hospitals in Isfahan in 2020. The data were collected using semi-structured in-depth interviews with 12 nurses who had palliative and end-of-life care experiences for infants and families. The nurses were selected using purposive sampling. The duration of each interview varied from 25 to 50 minutes. Data were analyzed using conventional qualitative content analysis conducted inductively with Graham and Lundman’s approach. The criteria proposed by Guba and Lincoln were used to ensure the credibility and reliability of the data. Results: Three main categories were extracted from the data, including unfavorable conditions (subcategorized into “unsuitable physical environment” and “shortage of nurses”), nurse's mental problems (with the subcategories of “nurses’ mental problems in providing neonatal care” and “nurses’ mental problems in providing family care”) and challenges ahead (with the subcategories of "parental presence challenge” and “doctor's instructions challenge”). Conclusions: The findings of the present study revealed the barriers to palliative care for infants and families in NICUs. Given the importance of palliative care in NICUs, effective measures must be taken to overcome these barriers.