Abstract: Objective To analyze the distribution of late-onset sepsis (LOS) pathogens and the influence factors of LOS on very low and extremely low birth weight infant, and to provide reference for the clinical treatment. Methods The clinical data of 166 cases of very low and extremely low birth weight infant in our hospital from December, 2014 to September, 2017 were retrospectively analyzed, and they were divided into non-LOS group (74 cases) and LOS group (92 cases) according to the occurrence of LOS. In the LOS group, 55 cases was diagnosed LOS and 37 cases were confirmed. The clinical features and mortality were compared between the two groups. The distribution of pathogens in LOS group was analyzed, and the influencing factors of LOS were assessed by binary logistic analysis. Results There were significantly differences in the small for gestational age (SGA), neonatal asphyxia, neonatal respiratory distress syndrome (NRDS), patent ductus arteriosus (PDA), peripherally inserted central catheter (PICC), mechanical ventilation, gestational age, weight, duration of parenteral nutrition and hospital time between the two groups (P<0.05). The rate of fatality in LOS group was 14.13% (13/92), and the non-LOS group was 4.05% (3/74), and there were significantly differences in the rate of fatality by comparison (P<0.05). The pathogens of the children in LOS group were 45 strains, among which, the gram-positive bacteria accounted for 31.11% (14/45), the gram-negative bacteria accounted for 62.22% (28/45), and the fungi accounted for 6.67% (3/45).The binary logistic analysis showed that the main influencing factors of LOS were the neonatal asphyxia, PICC, gestational age and duration of parenteral nutrition. Conclusion Gram-negative bacteria are common pathogenic bacteria of LOS on very low and extremely low birth weight infant, and the neonatal asphyxia, PICC, gestational age and duration of parenteral nutrition were the main influencing factors of LOS.