Introduction: Perinatal hypoxic-ischemic cerebral injury remains an important issue partly because it is the most clearly recognized cause of cerebral palsy. Multi-organ dysfunction (MOD) is one of four consensus based criteria for the diagnosis of intrapartum asphyxia. The theoretical concept behind MOD is the diving reflex. Objectives: the aim of this study was to assess the patterns of involvement of each organ/system and combinations of involvement of these organs in infants with post-asphyxial hypoxic-ischemic encephalopathy (HIE). Patients and methods: This is a retrospective study carried out on 100 hypoxic ischemic neonates who were admitted on their first day of life to the Neonatal Intensive Care Unit (NICU) in Kasr El Aini Hospital, Cairo University, Egypt. Results: Multi-organ dysfunction (MOD) occurred in 74% of our patients with renal dysfunction the commonest to occur (64%). Two-organ dysfunction occurred in 49% of patients followed by one-organ dysfunction in 38% of patients with MOD. Mortalities increased as the number of organ dysfunction increased. Conclusion: We found evidence in support of the MOD criterion in the definition of asphyxia, with renal dysfunction being the most commonly occurring dysfunction.