It is recognised that substantial associations exist between personality and distress, and that distress is a primary contributor to the onset of mood related disorders. This study examined the relationship between aspects of personality and distress, and explored whether dispositional mindfulness evidenced a significant moderation effect. Participants (N = 165) were recruited through a virtual learning environment and a social media website and completed an online survey which included the Friedberg Mindfulness Inventory, the Kessler Distress Scale and the Five Factor Personality Inventory. Neuroticism was the only personality trait that predicted non-specific psychological distress (NPD). A hierarchical multiple regression analysis revealed mindfulness moderated the neuroticism – NPD relationship with a substantial standardised beta weight and large effect size. Thus, lower NPD was found in individuals with higher dispositional mindfulness even in the presence of high neuroticism scores. This study presents an initial stage in examining the benefits of mindfulness in relation to neuroticism's vulnerability to NPD and may instigate further research into targeted mindfulness interventions.