Introduction: To evaluate variations in platelet count and platelet indices-mean platelet volume (MPV) and platelet distribution width (PDW) in neonatal sepsis. Methodology: This study was conducted over a period of one year in Neonatal Intensive Care Unit of Mata Chanan Devi Hospital, New Delhi. Neonates with confirmed as well as probable sepsis were included in the study. Platelet count, MPV and PDW were monitored three times: at diagnosis (1 st day), 3 rd day and 7 th day of sepsis. Results: Among 100 cases, culture proven sepsis was present in17 neonates. Fungal sepsis occurred in 2 cases (11.76%), 7 neonates (41.18%) had gram positive sepsis and 8 neonates (47.06%) had gram negative sepsis. Thrombocytopenia was present in 38% and thrombocytosis in 6% cases. Mild thrombocytopenia was noted in 55.26%, moderate thrombocytopenia in 31.58% and severe thrombocytopenia in 13.16% babies. Culture positive neonates had high prevalence of thrombocytopenia. High mortality was found in moderate to severe thrombocytopenic neonates, and these babies also had high MPV and high PDW. Conclusions: Thrombocytopenia was more common than thrombocytosis in neonatal sepsis. Prevalence of thrombocytopenia was significantly high in culture proven sepsis (64.7%). There was statistically significant difference in mean platelet count on day 1, day 3 and day 7 of sepsis among culture positive and culture negative neonatal sepsis. Neonates with culture proven sepsis had high MPV on day 7 and high PDW on day 1 of sepsis. There was high MPV and high PDW in neonates who developed thrombocytopenia and also in expired babies. Platelet count and platelet indices can be used as early diagnostic and prognostic biomarkers for neonatal sepsis.