Key Points • The RA patients in the present study had 1.7 mL/kg/min lower mean estimated cardiorespiratory fitness (CRF) compared to healthy controls. • Mediation analysis demonstrated that physical symptoms and negative emotions mediated 74% of the total negative effect of RA on estimated CRF in a combined, adjusted model. • This suggests that both physical and psychological factors should be addressed when supporting RA patients in improving their CRF.