Psychological flexibility, the capacity to be open to any internal stimuli and act in accordance with valued ends, has been identified as an explanatory variable in how people cope with body concerns. The role of psychological flexibility is unexplored in adults with an atypical appearance due to a health condition, injury, or medical treatment (collectively visible difference), who often encounter multiple day-to-day body image threats. Testing two core components of psychological flexibility, namely experiential avoidance (a desire to avoid or get rid of unpleasant internal experiences) and cognitive fusion (taking thoughts literally), can also provide a more precise theoretical model, with clearer implications for psychological intervention. This survey study investigated whether each psychological flexibility component mediated the relationship between body evaluation and two unhelpful body image coping strategies (behavioural avoidance and appearance-fixing behaviours) in 220 adults with various causes of visible difference. Controlling for demographic variables and subjective noticeability of visible difference, results suggest that cognitive fusion partially mediated the relationship for both body image coping strategies, and experiential avoidance partially mediated behavioural avoidance but not appearance-fixing behaviours. Cognitive fusion may be a particularly important cognitive process in the mechanisms underpinning unhelpful body image coping strategies in this population.