Chorioamnionitis is a known risk factor for neurological damage in newborns. The present study aimed at assessing the changes in cerebral blood flow velocity (CBFV) in early-onset neonatal sepsis (EONS) and determining its predictive value as well as prognostic significance. Inborn neonates with antenatal risk factors for chorioamnionitis were followed up for development of EONS, diagnosed by presence of clinical signs along with positive blood culture and/or elevated interleukin-6 (IL-6) concentrations (≥50 pg/mL) in umbilical cord blood. Comparison group was formed by asymptomatic neonates who had risk factors for chorioamnionitis but did not develop EONS and cord blood IL-6 concentrations were <50 pg/mL. CBFV (resistance and pulsatility indices, peak systolic flow velocity, and vascular diameter) of internal carotid, vertebral, and middle cerebral arteries was assessed by transcranial Doppler ultrasonography within 24 h of birth. The babies were kept under clinical and radiological follow-up for a minimum period of 6 months. Data were analyzed by SPSS 16.0. Final study group contained 55 neonates with sepsis and 35 asymptomatic control neonates. Blood culture was positive in 27 babies of the sepsis group with a preponderance of Gram-negative bacterial isolation. Significantly lower resistance, vasodilatation, and higher blood flow were noted in all the cerebral arteries of the sepsis group. Increase in CBFV was correlated with elevated IL-6 concentrations. CBFV parameters showed significant predictive accuracy as early diagnostic markers of EONS. Among the sepsis group, 14 patients showed signs of intracranial hemorrhage during the hospital stay of which four expired and six showed signs of ventricular dilatation during follow-up. These patients had significantly higher CBFV compared to those who survived. Assessment of CBFV at early hours of birth can be adopted as an additional bedside, non-invasive investigation with immediate diagnostic and late prognostic significance.