Background: A retrospective study was conducted to assess the mediation role of low birth weight, and low ponderal index between the preeclampsia, placenta previa, and neonatal mortality in the tertiary hospital of Hubei Province, China. Methods: A total of 12772 neonatal births were included for data analysis. Birth weight, birth length, and neonatal mortality were recorded after birth. Sobel test based on mediation regression was used to evaluate the effect of mediator variables. Results: Approximately, 383 (3%) and 409 (3.2%) women experienced preeclampsia and placenta previa respectively. After adjusting for covariates, the indirect effect of preeclampsia on neonatal mortality mediated by low birth weight and low ponderal index was [β 2.59 (95% CI: 0.74 – 4.44)], and [β 3.94 (95% CI: 1.50 – 6.38)] respectively. Moreover, the indirect effect of placenta previa on neonatal mortality mediated by the low birth weight was [β 1.74 (95% CI: 0.16 – 3.31)], and low ponderal index was [β 3.21 (95% CI: 0.95 – 5.48)]. The estimated mediation proportion between the preeclampsia and neonatal mortality accounting for possible mediation by low birth weight and low ponderal index was 44.5% and 34.5% respectively. Furthermore, 47.9% by low birth weight and 33.2% by low ponderal index mediate the association between placenta previa and neonatal mortality. Conclusion: Low birth weight, and low ponderal index partially mediates the association between preeclampsia, placenta previa and neonatal mortality.