Late-onset sepsis (LOS) is a major problem in the NICU associated with high morbidity and mortality. The study aimed to asses the diagnostic value of serum amyloid A protein (SAA) during late-onset sepsis in preterm and full term neonates. In this study, the level of SAA was measured in the serum of neonates with LOS presented after the 7th day to the NICU (cases) and was compared with the level of SAA in healthy neonates (controls) and compared with other tests usually used to diagnose sepsis in NICUs (TLC, CRP, I:T ratio and platelets count ). SAA level was significantly higher in the cases than its level in the controls , and continued to be elevated after initiation of treatment by 48-72 hours in the cases compared to controls. The level of SAA in the Gram negative group was significantly elevated than the level of SAA in the Gram positive group. SAA level was significantly elevated in septic neonates who were preterms, those with low birth weight and those with low Apgar score due to increase incidence of sepsis in these groups. Comparing SAA data to the tested other markers of sepsis including CRP, TLC, I: T ratio and platelets count, it was found that SAA was the most sensitive (86%). As regarding specificity, SAA was most specific than CRP, TLC and PLT, but less in specificity than I: T ratio (100%). The SAA protein level in the non survivors showed a high significant elevation compared to the discharged. There was a highly significant positive correlation between SAA and each of CRP and I: T ratio, a significant negative correlation between SAA and PLT count, and a non significant positive correlation was observed between SAA and TLC in the cases. Also SAA protein showed highly significant positive correlation with BUN and creatinine in the same group. In conclusion: The SAA protein could be used as an accurate marker in diagnosis of late onset neonatal sepsis, the level of SAA in the Gram negative group was significantly elevated than its level in the Gram positive group and in the non survivors more than in the improved cases. SAA was the most sensitive marker in comparison with CRP, TLC, I: T ratio and platelets count in diagnosis of late onset sepsis, its specificity was high in comparison with CRP, TLC, and platelets count but lower than that of I: T ratio.