Endometriosis is a chronic systemic disease affecting 1 in 10 people assigned female at birth, that can result in appearance-based and functional bodily changes which can negatively impact body image. Empirical evidence supports the body dissatisfaction-driven hypothesis that negative body image leads to greater depressive symptoms; but potential underlying mechanisms are under-researched. This prospective study investigated the mediating role of two theoretically-derived intervening factors, self-esteem and rumina-tion, in individuals living with endometriosis who typically report high rates of body image concerns and depressive symptoms. Initially, 996 participants completed the first online survey (T0) assessing demo-graphic, medical and psychological factors. Of these, 451 completed surveys at 1-month (T1) and 2-months (T2) follow-up assessing self-esteem, rumination and depression. Bootstrapped analyses with full -in-formation maximum likelihood estimation indicated that poor body image (T0) predicted greater depres-sive symptoms over time (T2). Self-esteem (T1), but not rumination (T1), mediated the body image -depression relationship. These results provide support for the body dissatisfaction-driven hypothesis and further identify that self-esteem is a key meditating factor. This highlights the importance of addressing self-esteem in body image focused interventions.(c) 2022 Elsevier Ltd. All rights reserved.