Abstract: Objective To investigate the expression of cerebrospinal fluid vitamin D binding protein (VDBP) and Tenascin-C in children with acute bacterial meningitis (ABM) and its clinical significance. Methods A total of 150 ABM children who were admitted to Department of Pediatrics, Yulin Hospital, the First Affiliated Hospital of Xi'an Jiaotong University, from January 2021 to October 2024 were enrolled. According to whether complications occurred during hospitalization, the patients were divided into a complication group and a non-complication group. According to the prognosis at discharge, the patients were again divided into a poor prognosis group and a good prognosis group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of VDBP and Tenascin-C in cerebrospinal fluid. Multivariate unconditional logistic regression analysis was performed to evaluate the relationship between cerebrospinal fluid VDBP and Tenascin-C levels and poor prognosis in children with ABM. Receiver operating characteristic (ROC) curves were plotted to assess the predictive value of cerebrospinal fluid VDBP and Tenascin-C levels for complications and poor prognosis in children with ABM. Results Among the 150 children with ABM, 57 developed complications, with an incidence of 38.00% (57/150). Compared with the non-complication group, the levels of cerebrospinal fluid VDBP and Tenascin-C were significantly increased in the complication group (P<0.05). The area under the ROC curve (AUC) for the combined prediction of complications using cerebrospinal fluid VDBP and Tenascin-C was 0.873, which was higher than that of VDBP (0.788) or Tenascin-C (0.798) alone (P<0.05). Compared with the good prognosis group, the levels of cerebrospinal fluid VDBP and Tenascin-C were significantly increased in the poor prognosis group (P<0.05). Multivariate logistic regression analysis showed that recurrent seizures, presence of complications, reduced cerebrospinal fluid glucose/blood glucose ratio, increased VDBP levels, and increased Tenascin-C levels were independent risk factors for poor prognosis in children with ABM (P<0.05). The AUC for the combined prediction of poor prognosis using cerebrospinal fluid VDBP and Tenascin-C was 0.900, which was higher than that of VDBP (0.806) or Tenascin-C (0.817) alone (P<0.05). Conclusions Elevated levels of cerebrospinal fluid VDBP and Tenascin-C are closely associated with the occurrence of complications and poor prognosis in children with ABM. The combined detection of VDBP and Tenascin-C has a high predictive value for complications and poor prognosis in children with ABM.