Objective: Hypoxic-Ischemic Encephalopathy (HIE), remains a serious condition, causing significant mortality and long-term morbidity. In spite of major advances in monitoring technology and knowledge of fetal and neonatal pathologies perinatal asphyxia remains a major concern. Serum Amyloid A (SAA) is an acute phase inflammatory marker that is closely associated with ischemic injuries. This study was aimed to evaluate the serum level of SAA in neonatal HIE and its concentration correlates with the severity of encephalopathy. Study Design: We conducted a prospective case- control study on 44 full-term neonates; 24 cases with evidence of perinatal compromise and 20 healthy controls. Blood samples were collected from cases and controls at postnatal day 1 and day 7, and SAA was measured by ELISA. Results: SAA concentrations (mgml-1) were significantly increased in cases when compared with controls at day 1 and at day 7 (p