Background This study investigated the relationship among negative affect, body image disturbances (BID), and interpersonal problems, and the mediating effect of self‐esteem in a group of treatment‐seeking obese individuals. Methods Four hundred twenty‐two obese patients (85 males and 337 females) completed standardised measures that assessed negative affect, BID, self‐esteem, and interpersonal problems. Results Structural equation modelling showed that obese individuals with greater negative affect and BID reported higher interpersonal problems and that self‐esteem mediated the relationships among negative affect, BID, and interpersonal problems. Conclusions The mediating role of self‐esteem in the relationship between interpersonal functioning and psychological distress needs to be considered when selecting psychologically based interventions that aim to improve the well‐being of treatment‐seeking obese patients.