Background: Neonatal sepsis is a major health problem. Thrombocytopenia in neonates is a serious disorder affecting 1%-5% of neonates at birth and up to 50% of the neonates receiving intensive care. Neonates with this disease are at risk for hemorrhage, particularly intraventricular hemorrhage, negative neurodevelopmental outcomes and increased mortality. One of the chief reasons of neonatal thrombocytopenia is sepsis. Objectives: We aimed to explore the different grades of severity thrombocytopenia and their relationship with diverse types of organisms in blood cultures from neonatal sepsis patients highlighting their prognostic role. Methodology: This is a retrospective study of one year duration including data of culture proven neonatal sepsis patients admitted at the neonatal intensive care unit (NICU), in Cairo University Pediatric Hospital. Results: We studied 314 neonates diagnosed with sepsis grounded on clinical signs and/or microbiological laboratory results. 171 had positive blood culture; 124 of them were Gram negative bacteria (72.5%) and 47 were gram positive ones (24.4%). Klebsiella spp. was the most repeatedly encountered organism among all positive blood cultures (n=74) (43.3%) and coagulase negative staphylococci was the most frequently isolated Gram positive bacteria (n=22) (12.9%). A total of 134 patients had thrombocytopenia; its degree of severity was ranging from mild, moderate, to severe in 101, 25, and 8 neonates, respectively. We found no association between the severity of thrombocytopenia and the type of organism in blood culture; however, thrombocytopenia was significantly higher among neonates with Gram negative blood cultures (p 0.001). Poor outcome has a statistically remarkable correlation with gestational age and reduced platelet count (p value <0.001). There is a 2.131 increased probability of developing thrombocytopenia in patients with neonatal sepsis. Conclusion: The percentage of thrombocytopenia reported in the blood culture proven sepsis episodes highlights the extent of the problem. The present study found a greater percentage of thrombocytopenia among neonates with Gram negative sepsis compared to those with Gram positive sepsis. Sepsis with Klebsiella spp. needs superior consideration regarding platelet monitoring.