The objective of this study was to use structural equation modeling (SEM) to examine the relationships between factors of cognitive complaints in 427 adults with HIV receiving care from an AIDS service organization (ASO) in Alabama. A face-to-face interview assessed cognitive complaints, mood, self-perceived health status, and substance use. Direct and indirect paths were specified between years with HIV (chronicity) age, education, stress, self-perceived health status, substance use, and cognitive complaints. The final model fit the data well (GFI=.95; AGFI=.92), revealing that age, education, substance use, self-perceived health status, and stress contributed directly or indirectly to cognitive complaints. Chronicity was only related to age, suggesting that duration of HIV may be of limited value in predicting cognitive complaints. These results demonstrate the complexity between the factors that influence cognitive complaints and offer possible solutions that health professionals can use to mitigate cognitive complaints in this population.