Blood cultures were still the gold standard for diagnosis, but they were difficult to obtain and took time. There was a need to identify and validate newer, less expensive investigations that can aid in diagnosing neonatal sepsis. For a study, researchers sought to determine whether platelet parameters, such as total platelet count (TPC), mean platelet volume (MPV), and the MPV/TPC ratio, could be used as diagnostic markers in neonatal sepsis. A prospective study was carried out in a tertiary care neonatal intensive care unit (NICU). Platelet parameters, such as TPC, MPV, and MPV/TPC, were compared between blood culture-positive septic neonates and non-septic neonates admitted to the NICU. Receiver operating characteristics (ROC) curves and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to assess the diagnostic accuracy of the platelet indices (NPV). During the study period, 43 sepsis neonates with positive blood cultures were compared to 54 non-septic neonates. The mean TPC, MPV, and MPV/TPC ratios were significantly different between septic and non-septic groups. MPV (cut-off >9 fL) sensitivity, specificity, PPV, and NPV values were 63.40%, 53.8%, 52.0%, and 65.11%, respectively. MPV/TPC ratio (>7.2) sensitivity, specificity, PPV, and NPV were 48.8%, 96.22%, 90.9%, and 70.42%, respectively. In the ROC analysis, the area under the curve (AUC) values for TPC, MPV, and MPV/TPC were 0.797, 0.641, and 0.809, respectively. The platelet indices MPV and MPV/TPC ratio could aid in the early detection of neonatal sepsis.