Moral disengagement is a useful construct for explaining disruptive behavior in adolescents, revealing differences between men and women. However, no research has been conducted on the association between clinical and psychological factors and the use of moral disengagement mechanisms. For this reason, this study analyzed sex differences and clinical predictors of moral disengagement mechanisms in teenagers. A quantitative, non-experimental, cross-sectional, and explanatory methodology was used. The participants were 354 adolescents between 14 and 18 years of age (M = 15.58, SD = 1.22) from two educational institutions in Manizales, Colombia. The moral disengagement scale (MMDS) was used along with self-esteem (RSES), impulsivity (BIS-11), despair (BHS), anxiety (BAI), and depression scales (BDI). A Student's t-test showed that men scored higher than women on all moral disengagement mechanisms. A multiple linear regression analysis by sex also revealed that impulsivity had an effect on moral disengagement in men, whereas the variables impulsivity, despair, and anxiety showed the highest effects explaining moral disengagement in women. The multiple linear regression model showed that impulsivity and sex had the strongest effects on the prediction of moral disengagement and its mechanisms. The results are considered to offer innovative theoretical explanations in a line of research aimed at linking psychological, clinical, and cognitive-social perspectives, with major implications for psychosocial intervention in adolescents © Copyright 2020 by Psykhe