To evaluate the validity of the Quality of Well-Being Scale (QWB) for studies of patients with human immunodeficiency virus (HIV) disease, 514 men were studied who were divided among four categories: Centers for Disease Control and Prevention (CDC) Group A (N = 272), CDC-B (N = 81), CDC-C (N = 47), and uninfected male controls (N = 114). The QWB and a variety of medical, neuropsychological, and biochemical measures were administered to all participants. When QWB scores were broken down by HIV group, the CDC-C group was significantly lower (.614) than the CDC-B (.679), CDC-A (.754), or control group (.801). The difference between Groups CDC-C and CDC-A was about .14 units of well-being, which suggests that individuals lose 1/7 equivalents of 1 well year of life for each year they are in Group CDC-C in comparison to the asymptomatic group (Group CDC-A). In comparison to the controls, this would equal a 1-year of life loss for each seven infected individuals. The QWB was shown to be significantly associated with CD4+ lymphocytes (p < .001), clinician ratings of neuropsychological impairment (p < .04), neurologists ratings of dysfunction (p < .001), and all subscales of the Profile of Mood States. Baseline QWB scores were significant prospective predictors of death over a median follow-up time of 30 months. Multivariate models demonstrated high covariation between predictors of QWB. It was concluded that the QWB is a significant correlate of biological, neuropsychological, neurological, psychiatric, and mortality outcomes for male HIV-infected patients.