Neurocognitive impairment (NCI) remains prevalent in HIV-infected subjects despite effective combination antiretroviral therapy (CART). In subjects without evidence of hepatic decompensation, NCI is also a feature of chronic HCV infection. The present study aimed to examine cerebral function and establish differences between HIV-HCV co-infected (HCVco) and HIV mono-infected (HIVmo) individuals. Neurologically asymptomatic subjects with chronic HCVco were eligible and underwent computerized neurocognitive testing (CogState; CogState Ltd, Melbourne, Australia), a dementia assessment [International HIV Dementia Scale (IHDS)] and memory assessment [the Prospective and Retrospective Memory Questionnaire (PRMQ)]. Historic control data were available for 45 HIVmo individuals and differences between study groups were assessed. Twenty-seven HCVco subjects were recruited. Plasma HIV RNA was <50 copies/mL in 25/27 of HCVco subjects and all HIVmo subjects and nadir CD4+ cell count (mean ± SD) was 214 ± 166 cells/µL and 180 ± 130 cells/µL, in HCVco and HIVmo subjects, respectively. No statistically significant differences in neurocognitive parameters or PRMQ scores were observed between groups. However, a trend towards poorer executive function score was observed in HCVco subjects (p 0.106). IHDS score (mean ± SD) was poorer in HCVco subjects (10.48 ± 1.25) vs. HIVmo subjects (11.51 ±0.76), (p <0.001). In a multivariate model, increasing age and HCVco were the only factors significantly associated with poorer IHDS scores (p 0.039 and <0.001, respectively). In HIV-infected subjects stable on CART, statistically significantly poorer performance in the IHDS score was observed in subjects with HCVco, although no differences were observed after neurocognitive testing or memory assessment.