We measured the levels of sFas and sFasL in CSF and serum of HIV-1 infected patients and related them to AIDS dementia complex (ADC). Specimens were obtained from 51 HIV-1 infected individuals (29 with ADC) and 39 HIV negative individuals. The sFas was detectable in all sera and 98% of CSF specimens. Measurable levels of sFasL were found in 79% of the CSF and 98% of sera samples. According to the presence or absence of ADC, we observed significant differences in CSF sFas (median and IQR 116, 132 vs. 30, 23 pg/ml, P<0.001) and sFasL (median and IQR 127, 290 vs. 15, 73 pg/ml, P<0.001) levels. The sFas in serum differed significantly between HIV-1 infected subjects and non-infected controls (P<0.001), with no correlation to ADC. On the contrary, sFasL in serum differed among HIV-1 infected subjects according to clinical signs of ADC. In the cross-sectional study, the number of cells present in CSF and CD4+ T cell counts in blood did not correlate to the levels of CSF sFas and sFasL. Interestingly, the number of HIV RNA copies in CSF correlated significantly to the levels of CSF sFasL (P=0.001) but not to sFas in the same compartment. Antiretroviral therapy reduced viral load and sFas levels in CSF in the majority of patients. sFas is a useful marker for ADC diagnosis and follow-up during antiviral treatment.