The most specific criterion for diagnosing neurosyphilis is a reactive CSF VDRL. Unfortunately, there are in Europe, including Poland small number of specialized laboratories for serological diagnosis of syphilis. Thus, CSF serology results are obtained with delay. Therefore, the decision on recommended therapy for neurosyphilis is taken on the basis of CSF basic tests. In this paper we attempt to determine the utility of CSF glucose concentration and its cut-off values in prediction of asymptomatic neurosyphilis. CSF and blood were collected from 55 HIV-uninfected patients with syphilis of unknown duration. Patients with neurosyphilis (14.5%) were characterized by higher CSF pleocytosis (p<0.0001), elevated CSF protein concentration (p<0.05) and lower CSF glucose concentration (p<0.0001). Multivariate regression analysis identified CSF pleocytosis and CSF glucose concentration as the two independent predictors of reactive CSF VDRL (p<0.0001). In the selected group of patients with CSF pleocytosis ≥5/µL (n=25) CSF glucose concentration ≤2.72 mmol/L was associated with 100% sensitivity (95%CI: 63–100%) and 100% specificity (95%CI: 75.3–100%) for reactive CSF VDRL. CSF glucose concentration may be particularly useful as a predictive marker of neurosyphilis in HIV uninfected patients with syphilis of unknown duration with CSF plecytosis ≥5/µL.