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Sex differences in cognition of HIV positive (HIV+) patients are controversial. We aimed to investigate the relationship between cognition, HIV status, and sex, in a highly homogenous cohort of young Romanians parenterally infected during early childhood.In total, 250 HIV+ participants were compared with age-matched HIV negative (HIV−) controls (n = 72) in a cross-sectional study. After standardized neurocognitive, psychological testing and medical evaluation, linear regression was used to assess the effect of sex and HIV on neurocognitive outcomes.Study participants were on average 23 years old with balanced sex distribution (% women = 52% vs. 43%). HIV− were more educated (12.7 vs. 11.6 years, P = 0.002).HIV+ status was associated with a lower global performance (β = −0.22, P < 0.001), after controlling for age and education. HIV+ women had better previous and current HIV-associated markers. The effect of HIV on global cognition did not differ between sexes in most cognitive domains (β = 0.07, P = 0.14). An interaction between sex, HIV status, and cognitive functioning was found in the psychomotor domain. HIV+ women had worse motor skills than HIV− women (β = −0.32, P < 0.001) suggesting a specific effect of HIV on motor functioning in women only. Moreover, current CD4+ less than 200 cells/μl (P = 0.013) and longer time lived with CD4+ less than 200 cells/μl (P = 0.023) were negatively correlated with the motor scaled score in women (β = −0.22, P = 0.034).Despite less advanced disease in women, long-term HIV infection has an equally detrimental effect on cognitive performances of both sexes, in all cognitive domains, except the psychomotor domain where women are preferentially affected.