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The purpose of this study was to examine the impact of neurocognitive and emotional distress and immune system dysfunction on quality of life in women with HIV.Thirty-six HIV-seropositive women were administered measures of mood status (Profile of Mood States), quality of life (Multidimensional Quality of Life Questionnaire for Persons with HIV) and cognitive function. CD4 cell counts were obtained as an indicator of immune system status.Regression analyses revealed that independent of severity of emotional distress, neurocognitive deficits on measures of executive control and speed of information processing were associated with reduced quality of life. Emotional status also was associated with quality of life and together with neurocognitive performance accounted for most of the variance associated with quality of life. Reduced CD4 cell count was significantly associated with neurocognitive deficits, but not severity of emotional distress or quality of life.Quality of life among women who are infected with HIV is strongly influenced by both neurocognitive and emotional status, as women with the greatest neurocognitive impairment and emotional distress report the poorest quality of life.