Fatigue is one of the most prevalent and troubling symptoms suffered by people with HIV infection. As part of a pilot study to examine physiological and psychosocial correlates of fatigue, the authors report results from a sample of 40 HIV-positive men and women who collected three saliva samples each over the course of a day. Few in the sample exhibited the normal salivary cortisol slope (a peak in the morning and falling throughout the day). There were four groups (N = 36) based on salivary cortisol plots: a normal downward trend (n = 7), an afternoon peak (n = 15), an afternoon drop (n = 9), and an upward trend (n = 5). The data in each of these groups were then analyzed on the key variables of sex, age, depression, state/trait anxiety, fatigue severity, CD4 count, and HIV viral load; the group that had an upward trend in cortisol values had a tendency toward more depression, more state and trait anxiety, higher fatigue severity, and higher HIV viral load. However, they also trended toward higher CD4 counts than the other three groups. The need to compare additional variables over a period of time is discussed.