Abstract: Objective To evaluate the predictive value of neonatal sequential organ failure assessment (nSOFA) score for predicting the mortality in very low birth weight (VLBW) neonates with late-onset sepsis (LOS).Methods It was a single-center, retrospective, case-control study. A total of 95 VLBW infants with LOS, who were admitted to the Intensive Care Unit, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital from 2018 to 2021 were selected. Their nSOFA scores at diagnosis and at 6 h post-diagnosis were analyzed. According to the clinical outcome after continuous use of antibiotics, the patients were divided into two groups:a death group and a survival group. The efficiency of nSOFA to predict the mortality of LOS in VLBW neonates was evaluated by a receiver operating characteristic curve.Results The nSOFA scores were statistically different between the death group and the survival group at 6 h post-diagnosis (P<0.01), without statistical difference at diagnosis (P>0.05). For the nSOFA score prediction model, the area under the curve (AUC) at 6 h post-diagnosis was 0.873 (95%CI 0.729-1.00, P=0.000), and 0.541 at diagnosis (95%CI 0.32-0.77, P=0.69). The maximum Yoden index at 6 h post-diagnosis was 0.687, and the corresponding decision threshold was 6.5.Conclusions The nSOFA score as 6 h post-diagnosis can predict the mortality of LOS in VLBW infants. Monitoring nSOFA is useful for the improvement of neonatal sepsis outcomes.