Both depression and neurocognitive compromise are commonly observed among persons infected with the Human Immunodeficiency Virus (HIV). To date, the majority of studies have failed to find a consistent relationship between mood and cognition among HIV-seropositive (HIV+) individuals, suggesting that these constructs are independent of one another. However, depression is a multi-dimensional syndrome and its measurement often utilizes multi-factorial instruments containing cognitive, affective, somatic, and motivational components. The degree to which various symptoms or dimensions of depression might be related to neuropsychological performance in HIV-1 infection is not typically explored and was a main objective of the current study. A sample of 247 HIV+ persons completed both a comprehensive neurocognitive battery and the Beck Depression Inventory (BDI) as part of a standard clinical evaluation at a major community hospital. To examine the dimensionality of the BDI, a principal components analysis was conducted which suggested a three-factor solution comprised of factors representing Self-Reproach (SR), Mood-Motivation Disturbance (MM), and Somatic Disturbance (SOM). The relationship between each of these three factors and neurocognitive performance was examined using both regression and analysis of variance techniques. These analyses showed the MM factor, more so than either the SR or SOM factors, to be associated with several aspects of neurocognitive performance, including verbal memory, executive functioning, and motor speed. These findings suggest that certain items on depression rating scales may be more indicative of central nervous system (CNS) involvement than others. The association between disturbance in mood and motivation and neurocognitive compromise may suggest that each are sequelae of disease specific mechanisms.