Research on pain in autism spectrum disorder (ASD) is in its infancy, with almost nothing known about how individual differences may predicting pain response in ASD. In the present study, 45 adults (28 male, age 22-48 years) with diagnoses of autism and intellectual delay were observed during vaccination or dental cleaning and their pain behaviours coded and measures of autism symptom severity, anxiety, depression and obsessivity taken. Our findings showed that greater autism severity predicted greater pain response which was partially mediated by anxiety and depression. These data suggest that mental health symptoms are important when considering pain response in autism. Mood must therefore be considered in future research on pain in ASD as well as clinical pain management.