This study focused on neurocognitive disorders associated with HIV infection, characterizes the most affected neuropsychological domains and their potential as factors related with depression. 130 HIV-positive individuals with CD4 >200 cells/mm(3), undetectable viral load, treated with HAART and with all kinds of risk behaviors were included. A structured interview composed by seven sections was used and relevant clinical and laboratory data was assessed. For the neuropsychological and depression assessment the HIV Neurobehavioral Research Center (HNRC) Battery and Hamilton Rating Scale for Depression (HAM-D) were chosen. Univariate nonparametric statistics and multivariate regression model were performed. Among 34% of depressed subjects, 20.7% had attempted suicide, 45.4% were under psychiatric medication and only 19% had no diagnostic criteria for HIV Associated Neurocognitive Disorders (HAND). The effect of depression on cognitive function revealed a significant deterioration in five of the eight measures. In the multivariate analysis, five variables significantly determined depression: sex, social class, antidepressant medication, history of suicide attempt and Dexterity and motor speed (neuropsychological test battery). Despite good patient adherence to treatment (HAART and antidepressive) and good immune status, the prevalence of HAND and depression are high and suggest a significant relation between severity of depression and cognitive functioning.