Abstract The aim of this study was to determine whether self-esteem and adjustment to disease can mediate the association between pain and psychological well-being in patients with Rheumatoid Arthritis (RA). Coefficients of correlation, multiple linear regressions and Structural Equation Model (SEM) were employed in order to examine the direct and indirect relationships between pain, self-esteem, adjustment to disease and psychological well-being in a sample of 160 recently-diagnosed RA-patients. The outcomes of the analyses indicate that self-esteem and adjustment to disease are important links between pain and psychological well-being. Moreover, the results suggest the increasing importance of personality variables in mediating the relationship between pain and psychological well-being as the disease advances. The findings provide evidence for considerations that psychosocial interventions, focused on increasing the self-esteem and improving the adjustment to disease, may reduce the impact of pain on patients' psychological well-being and quality of life in general