Objectives: This study aimed to examine if autonomy-connectedness, capacity for self-governance under the condition of connectedness, would mediate sex differences in symptoms of various mental disorders (depression, anxiety, eating disorders, antisocial personality disorder). Method: Participants (N = 5,525) from a representative community sample in the Netherlands filled out questionnaires regarding the variables under study. Results: Autonomy-connectedness (self-awareness, SA; sensitivity to others, SO; capacity for managing new situations, CMNS) fully mediated the sex differences in depression and anxiety, and partly in eating disorder -(drive for thinness, bulimia, and body dissatisfaction) and antisocial personality disorder characteristics. The mediations followed the expected sex-specific patterns. SO related positively to the internalizing disorder indices, and negatively to the anti-social personality disorder. SA related negatively to all disorder indices; and CMNS to all internalizing disorder indices, but positively to the anti-social personality disorder. Conclusion: Treatment of depression, anxiety, but also eating disorders and the antisocial personality disorder may benefit from a stronger focus on autonomy strengthening.