Objectives <p>Lipoedema is a chronic disorder primarily affecting women. Often mistaken for obesity due to its characteristic build-up of fat cells in the legs and sometimes arms, lipoedema leaves women vulnerable to social stigma. This study investigated the role of fears of compassion and depressive symptoms in the context of weight stigma and internal weight bias in women with lipoedema.</p> Preregistration <p>This study is not preregistered.</p> Method <p>Cross-sectional data from an international online survey with 843 women with lipoedema were analysed using structural equation modelling to assess the relationships between experienced weight stigma, internal weight bias, fears of compassion and depressive symptoms (PHQ-9).</p> Results <p>Greater experienced weight stigma and internal weight bias were linked to increased fears of compassion. Experienced weight stigma most strongly correlated with fears of compassion from others (<i>p</i> &gt; 0.001), while internalised weight bias most strongly correlated with fears of self-compassion (<i>p</i> &gt; 0.001). In turn, greater fears of compassion from the self (<i>p</i> &gt; 0.001) and others (<i>p</i> &gt; 0.001) but not fears of compassion for others (<i>p</i> = 0.566) were related to greater depressive symptom severity. Further, both experienced weight stigma and internalised weight bias were associated indirectly with depressive symptoms via fears of compassion (<i>p</i> = 0.001).</p> Conclusions <p>In lipoedema, fears of compassion from others and the self may be exacerbated in the presence of experienced weight stigma and internalised weight bias, leading to increased severity of depressive symptoms. Targeting fears of compassion and addressing negative self-perceptions surrounding body weight through psychological interventions may therefore support psychological wellbeing and outcomes for women with lipoedema.</p>