Background:Neonatal sepsis is a significant cause of neonatal mortality in developing countries. The aetiological agents and their antimicrobial susceptibility patterns are dynamic.Objectives: This study determined clinical features, aetiology, antimicrobial susceptibility and clinical outcome of neonatal sepsis in a Nigerian Tertiary Hospital.Methods: Neonates undergoing sepsis evaluation at a Nigerian Tertiary Hospital were included in the study. Demographic and clinical information were obtained using standard questionnaires. Blood samples were cultured on MacConkey, Blood and Chocolate agar. Isolated bacteria were identified based on morphology, Gram stain appearance and standard commercially prepared biochemical tests. Antimicrobial susceptibility testing was performed on Mueller-Hinton agar using the Kirby-Bauer method.Results: Eighty-five of the 180 neonates admitted during the study period were recruited. Fifty-five neonates presented with early-onset sepsis and 30 with late-onset sepsis. Culture-proven sepsis was detected in 19 (22.4%) neonates. The incidence of culture-proven sepsis in the hospital was 2.8/100 live-births. The most common clinical feature at presentation was respiratory distress. Gram-negative bacteria accounted for 78.9 percent of all isolates and were the only organisms encountered in earlyonset sepsis. Isolated pathogens were predominantly Klebsiella spp (31.6%), Enterobacter spp (21.1%) and coagulase-negative Staphylococci (15.8%). The isolates were most sensitive to ofloxacin. Gram-negative bacteria showed high resistance to cefuroxime and ampicillin. The case-fatality rate was 26%.Conclusion: Gram-negative bacilli, especially Klebsiella spp, was predominant. Neonatal sepsis persists as a cause of mortality in this region. Regular antimicrobial surveillance for empirical treatment remains an important component of neonatal care.