Neonatal sepsis is a leading cause of morbidity and mortality among newborns, representing a critical challenge for neonatal care worldwide. Timely and accurate diagnosis remains pivotal in reducing adverse outcomes, underscoring the need for reliable biomarkers. Angiotensin Converting Enzyme (ACE), a vital component of the renin angiotensin system, has emerged as a promising candidate due to its involvement in inflammatory pathways and immune modulation. This review comprehensively explores the serum levels of ACE in neonates with sepsis, focusing on its potential diagnostic and prognostic significance. We summerize findings from recent studies to elucidate the role of ACE in the pathophysiology of neonatal sepsis, particularly its correlation with disease severity, immune response, and clinical outcomes. The article critically evaluates methodologies employed in ACE measurement, variations in serum ACE levels across different populations, and their relationship with established sepsis markers. Moreover, we discuss the challenges and limitations in translating these findings into clinical practice, such as standardization of assays and the influence of confounding factors. Highlighting existing gaps in the literature, this review identifies key areas for future research, including longitudinal studies to validate the predictive value of ACE and its integration into multi marker diagnostic panels. By addressing these gaps, we aim to pave the way for more effective strategies in the early detection and management of neonatal sepsis. This comprehensive review offers valuable insights for clinicians, researchers, and policymakers, emphasizing the potential of ACE as a biomarker to improve neonatal sepsis outcomes.