Objectives Previous research has indicated that perfectionism may be an important antecedent of exercise dependence (Hagan, A. L., & Hausenblas, H. A. (2003). The relationship between exercise dependence and perfectionism. American Journal of Health Studies, 18, 133–137; Hausenblas, H. A., & Symons Downs, D. (2002a). Exercise dependence: a systematic review. Psychology of Sport and Exercise, 3, 89–123, Hausenblas, H.A., & Symons Downs, D. (2002b). How much is too much? The development and validation of the exsrcise dependence scale. Psychology and Health, 17, 387–404). To date, however, few studies have sought to examine the psychological processes that underpin this relationship. The purpose of the present investigation was to determine the degree to which self-oriented and socially prescribed perfectionism were associated with exercise dependence, and to ascertain whether the relationships were mediated by unconditional self-acceptance and labile self-esteem. Method Three hundred and seven middle-distance runners completed a multi-section inventory that included Hewitt, P. L., & Flett, G. L. [(1991). Perfectionism in the self and social contexts: conceptualization, assessment, and association with psychopathology. Journal of Personality and Social Psychology, 60, 456–470] Multidimensional Perfectionism Scale, Chamberlain, J. M., & Haaga, D. A. F. [(2001). Unconditional self-acceptance and psychological health. Journal of Rational Emotive and Cognitive Behavior Therapy, 19, 163–176] Unconditional Self-acceptance Scale, Dykman, B. M. [(1998). Integrating cognitive and motivational factors in depression: initial tests of a goal orientation approach. Journal of Personality and Social Psychology, 74, 139–158] Labile Self-Esteem Scale, and Ogden, J., Veale, D., & Summers, Z. [(1997). The development and validation of the Exercise Dependence Questionnaire. Addiction Research, 5, 343–356] Exercise Dependence Questionnaire. Results Structural Equation Modeling provided support for three hypotheses. First, that self-oriented perfectionism had a direct positive effect on exercise dependence. Second, that unconditional self-acceptance fully mediated the relationship between socially prescribed perfectionism and exercise dependence. Third, that labile self-esteem mediated the relationship between unconditional self-acceptance and exercise dependence. Multi-group invariance analysis further indicated that there were subtle variations in the nature of these relationships for male and female samples. Conclusions The findings from the present study indicate that both self-oriented and socially prescribed perfectionism may be critical antecedents of exercise dependence, but that the psychological mechanisms underpinning their association with exercise dependence may differ.