BACKGROUND: Post-neurosurgical bacterial meningitis (PNBM) is a severe complication in patients receiving neurosurgical treatments. Pathogens and neuroinflammation have been reported to influence metabolites in the microenvironment of the central nervous system. However, information about the relationship between neurotransmitter levels and PNBM is still limited. In this study, we aimed to investigate the diagnostic potential of neurotransmitters for PNBM in the patients with stroke. METHODS: In this study, a total of 66 stroke patients were recruited. Among them, 40 patients were complicated with PNBM. We profiled cerebrospinal fluid (CSF) levels of neurotransmitter precursors and metabolites using the targeted metabolomics method, which contained 26 precursors and metabolites of neurotransmitters, using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS). RESULTS: We found that 14 biomarkers were downregulated but 3,4-dihydroxyphenylacetic acid (DOPAC) was upregulated in the CSF of PNBM patients. Among the biomarkers, D-glutamine (AUC=1.000), Boc-D-Tyr-OH (AUC=0.9447), L(+)-arginine (AUC=0.9418), and DOPAC (AUC=0.9173) had strong diagnostic efficiency for PNBM. Bioinformatic analysis showed that tyrosine metabolism, butanoate metabolism, histidine metabolism, alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and tryptophan metabolism might be involved in the pathogenesis of PNBM. After reviewing previous studies, we found a probable diverse pathophysiological alteration between PNBM and community-acquired bacterial meningitis. CONCLUSIONS: In summary, we identified downregulated levels of D-glutamine, Boc-D-Tyr-OH, L(+)-arginine, and phenprobamate, and an upregulated level of DOPAC in CSF to have strong diagnostic efficiencies. The results also offered potential targets for the treatment of PNBM.