This study assessed psychological distress (PD) in men who have sex with men (MSM) accessing primary health clinics in Australia. Relationships between PD, HIV status and substance use were explored. A cross-sectional convenience sample of 250 MSM completed the Personality Assessment Screener (PAS). One-third (n = 83) scored in the PAS clinically significant range, suggesting significant mental health symptoms. Negative Affect (27 per cent clinically significant), Suicidal Thinking (29 per cent clinically significant) and Amphetamine use significantly positively correlated with PD. There were no significant differences between HIV diagnostic groups on PD. A third of MSM displayed PD. Psychological screening may provide valuable information for improving the psychological well-being of MSM, regardless of their HIV status.