Background: Neonatal sepsis is a critical condition posing a significant threat to newborns globally, particularly in developing countries. The non-specific symptoms and time-consuming traditional diagnostic methods highlight the need for rapid and reliable biomarkers. Recent studies suggest platelet count and indices such as MPV and PDW as potential indicators for early diagnosis of neonatal sepsis. Objective: This study aims to comprehensively analyze the diagnostic value of platelet count and indexes as biomarkers in neonatal sepsis and elucidate their correlation with the severity and mortality of the condition. Methods: A hospital-based prospective study was conducted at SVPPGIP & SCB MCH, Cuttack, involving 200 neonates with suspected sepsis. Platelet count, PDW, and MPV were measured and correlated with sepsis severity and outcomes. Statistical analyses were performed using SPSS software, with a significance set at P<0.05. Results: Of the 200 neonates studied, 60% exhibited thrombocytopenia, more prevalent in culture-positive cases. There was a noteworthy inverse relationship discovered between platelet count and sepsis severity, while MPV and PDW were higher in more severe cases. Gram-negative organisms were the most common cause of sepsis. Notably, severe thrombocytopenia was strongly associated with increased mortality. Conclusion: The study confirmed a significant association between platelet count and indices with neonatal sepsis severity and mortality. Platelet count, MPV, and PDW can serve as effective, rapid diagnostic and prognostic biomarkers, potentially improving early detection and outcomes in neonatal sepsis. Recommendations: Further multicenter studies are needed to validate these findings across diverse populations and clinical settings. Additionally, enhancing technical expertise at grassroots levels is crucial for the reliable application of these biomarkers in routine neonatal care. This research advocates for the integration of platelet indices in the diagnostic protocol for neonatal sepsis, promising improved patient management and outcomes.