This study aimed to identify the prevalence and predictors of current fatigue and fatigue at 1-year follow-up, in people with HIV. Participants were recruited from HIV outpatient clinics in London, England. We explored a range of bio-psychosocial factors associated with current fatigue severity, identifying the most salient factors in a multifactorial model. A prospective study explored the predictive value of specific psychological and behavioral factors in predicting fatigue severity at one year. Sixty-four of 131 (49%) participants met the criteria for clinically significant fatigue at baseline. Psychological and behavioral variables, but not immune-virologic markers or antiretroviral treatment, were associated with current fatigue severity. In the multifactorial model, catastrophizing and distress independently predicted current fatigue severity. Higher levels of fatigue at 1 year was predicted by baseline catastrophizing, symptom focusing, distress and sleep quality, when controlling for baseline fatigue, clinical and demographic variables. These findings suggest psychological and behavioral factors are important in the maintenance of fatigue in people with HIV and identify potential opportunities for treatment. Future interventions for fatigue in HIV should not only address anxiety, depression and distress but could be optimized by targeting psychological processes such as catastrophic thinking styles and symptom focusing.