To study the maternal risk factors and clinico-bacteriological profile of early onset sepsis (EOS), in a tertiary care neonatal unit. Relevant data of neonates born during the study period were obtained from their case records. A diagnosis of early onset sepsis was made if either clinical sepsis developed within 72 hours of life or if positive blood/CSF cultures were obtained in those with potential maternal risk factors. Statistical analysis was done using Odds Ratio or Chi-square and Fisher's exact t-test as applicable. Among 1743 live births, a total of 69 episodes of sepsis occurred in 65 neonates (43% culture proven) with an incidence of 37.2 per 1000 live births. The incidence of EOS was 20.7 per 1000 live births and it constituted 55.4% of overall sepsis. Among the perinatal risk factors assessed, a significant association of EOS with prolonged rupture of membranes, foul smelling liquor, dai (midwife) handling and maternal urinary tract infection was observed (p < 0.05). Among infants at risk of EOS, 20.6% developed sepsis compared to only 0.5% of those without these risk factors (p 0.001). Even among those at high risk such as low birth weight, preterm, and asphyxiated neonates, incidence of EOS was negligible in the absence of a maternal risk factor. Pneumonia (66.7%), shock (27.7%), metabolic acidosis (19.4%) and meningitis (8.3%) were the comorbidities seen among the cases. Culture proven EOS occurred in 41.6%, Pseudomonas being the commonest (60%) isolate. The case fatality rate was 19.4%. Screening for sepsis in an asymptomatic neonate is warranted only in the presence of a maternal risk factor even if the neonate is at high risk of developing sepsis due to associated problems of prematurity, low birth weight or asphyxia. Knowledge of likely causative organisms of EOS can aid in instituting prompt and appropriate therapy, in order to minimise morbidity and mortality.