Background neonatal mortality rates are high in infants with low or very low birth weight (VLBW) as they are prone to sepsis .Early onset sepsis (EOS) that occur at 48hr of life remains an important cause of illness and death in VLBW infants. Objective of the study is to analyze association of Neonatal birth weight and neonatal sepsis in Karachi population and to study their pathogen distribution in positive isolates. Methodology a prospective cross-sectional study took place in Karachi leading hospitals Darul sehat hospital and Abdus Samad hospital neonatal birth weight and neonatal blood culture sensitivity test were studied for positive sepsis .data were analyzed using SPSS applying Chi square test Results out of 120 neonate’s blood culture sensitivity test 12 neonates had positive sepsis. Weight of 6 neonates out of 12 positive was 2.1-3kg and other 6 neonates weight was 3kg. 3 isolates were streptococcus pneumonia and 9 were staphylococcus aureus. Conclusion Infants with positive sepsis are of healthy weights. Therefore, results found to have no significant relation in between neonatal birth weight and neonatal sepsis .EOS remains an uncommon yet important cause of morbidity and mortality among VLBW infants.