No study has tested the effectiveness of individualized cognitive behavioral therapy (CBT) interventions to reduce persistent nausea, pain, anxiety, and fatigue in patients on continuous antiretroviral therapy (ART). Our objective was to determine if CBT could reduce nausea, pain, anxiety, and fatigue in patients with HIV on ART. Men ages 40 to 56 years on ART (n = 18) at a suburban HIV clinic were randomly assigned to a control group or the CBT intervention. Usual adherence education and side-effect management were provided to both groups. Symptoms, health perception, medication adherence, and side-effect-reducing medication use were measured at four time points over 3 months. Participants in the intervention group rated usual fatigue and worst fatigue at 60 days, and nausea duration at 90 days significantly lower than controls (p < .05). Brief CBT training may reduce fatigue and nausea in patients with HIV undergoing ART.