The purpose of this study is to explore risk factors of acute placental inflammatory lesions and the potential postnatal serum biomarkers for predicting the severity of intrauterine infection in preterm infants. We performed a retrospective analysis of premature infants with or without acute placental inflammatory lesions and their mothers by chart review for clinical data and placental histopathology. The preterm infants with acute placental inflammatory lesions had a higher rate of premature rupture of membranes (PROM), a longer duration of PROM, and a higher level of serum sialic acid (SIA) than those of the non-inflammation group (all p < 0.001). According to the different inflammatory histological structures, preterm infants with funisitis had a dominant longer duration of PROM than others (p < 0.05), and their gestational age was youngest among all the infants (p < 0.05). Furthermore, they had the highest content of serum SIA above other groups. The preterm infants in the acute histological chorioamnionitis group showed a similar trend of clinical manifestation and laboratory parameters with the funisitis group. Moreover, the closer the placental lesions were to the fetus, the lower the gestational age of preterm infants was, and the higher the serum SIA content was. Conclusion: We utilized a simple and precise anatomically category method of placental inflammatory histopathology for pediatricians to distinguish the extent of fetal inflammatory response for representing early-onset infectious diseases of preterm infants. SIA might be one of the potential early-stage serum biomarkers to reflect the severe intrauterine infections and could guide the postnatal anti-infection treatment.