Background/Purpose: Disability and impairments in role functioning are common obstacles for many patients with RA. A combination of disease-related and psychosocial factors may contribute to limitations in functioning. The purpose of this research was to examine a model describing the interrelations among disease burden, mood disturbance, and disability as determinants of role limitations in patients with RA. It was expected that disease burden would be negatively associated with role functioning directly and/or indirectly through the potential mediators of mood disturbance and disability. Methods: The data of 103 participants were drawn from baseline of a randomized comparative efficacy trial of psychosocial interventions for RA. In the hypothesized model, disease burden (total joint score and disease activity items from the Rapid Assessment of Disease Activity in Rheumatology) directly and indirectly predicted role functioning (physical role and social functioning from the Short Form-36) through negative mood (Center for Epidemiological Studies Depression Scale) and disability (large-limb gross movement and small-limb fine movement from the Health Assessment Questionnaire Disability Index). EQS 6.1 was used to evaluate the structural model. Data screening revealed a violation of multivariate normality, therefore, the ML robust test statistics, which correct for non-normal data, are reported. Results: The hypothesized model provided a good fit of the data, CFI = .975; S-B χ²(29) = 38.12, p = .120; RMSEA = .056. However, the Wald test indicated removal of the path from mood disturbance to disability (β = -.08, p = .421). As such, along with theoretical plausibility, this path was removed. The fit of this more parsimonious model was similar, CFI = .976; S-B χ²(30) = 38.60, p = .135; RMSEA = .053, and the final model is depicted in Figure 1. Greater disease burden predicted mood disturbance and higher levels of disability. In turn, mood disturbance and disability related to lower levels of role functioning. Partial support was found for the hypothesis that mood disturbance and disability mediate the relation between disease burden and role functioning. Specifically, as a sole predictor, the effect of disease burden on role functioning was significant (β = -.68, p < .001). Further, this effect was significantly reduced when mood disturbance (β = -.49, p < .001; Sobel Z = -2.33, p = .020) and disability (β = -.45, p = .007; Sobel Z = -2.08, p = .038) were entered in the model, indicating that each independently partially mediated the relation between disease burden and role functioning. Conclusion: The findings from this study confirmed the importance of a multi-dimensional framework in evaluating disability and role functioning in RA using a structural equation approach. Mood disturbance and disability play major roles in explaining role limitations along with patient-reported disease burden.