OBJECTIVE: To determine the frequency, degree and associated features of fatigue among Hispanic (H), African American (AA) and Caucasian (C) patients with recent onset (< or = 5 yr) systemic lupus erythematosus (SLE) at their baseline evaluation. METHODS: H (n = 69), AA (n = 83) and C (n = 71) patients from the LUMINA (LUpus in MInority populations: NAture vs Nurture) cohort were studied. Fatigue [Fatigue Severity Scale (FSS)] was defined as present if FSS score > or = 3.0. Variables from functional, clinical, sociodemographic, health behaviors, behavioral and psychological and immunogenetics domains were ascertained at study entry. Associations were examined using regression models. RESULTS: Eighty-six percent (85.7%) of patients reported having fatigue (82.6% H; 85.5% AA; 88.7% C); median FSS score, 5.3. Factors from the psychological and clinical domains were primarily associated with FSS; immunogenetic (HLA Class II phenotypes) features were not. Increased fatigue was strongly associated with decreasing function, both physical and mental. Variables associated with significantly greater degree of fatigue at baseline in the multivariable stepwise model in order of decreasing additional partial R2 explained included: abnormal illness-related behaviors, older age, higher self-reported pain, greater degree of helplessness, greater disease activity, Caucasian race, and lacking health insurance (model R2 = 37%). CONCLUSIONS: Fatigue is one of the most prevalent clinical manifestations of SLE across all ethnic groups. The perception of fatigue severity in SLE may be multifactorial in origin, including psychosocial factors and disease activity. If these prove causal, knowledge of their contribution may suggest therapeutic and/or behavioral interventions, which could ameliorate this pervasive and often incapacitating symptom of SLE.