COVID-19 social distancing mandates increased social isolation, resulting in changes in pain severity and interference among individuals with chronic pain. Differences in personality (e.g., introversion/extraversion) may modulate responses to social isolation. We examined the influence of introversion on reported social distancing-related increases in pain interference and assessed for mediators of this relationship. Individuals with chronic pain (n = 150) completed validated questionnaires 4–8 weeks after implementation of social distancing mandates. Introversion/extraversion was measured using a subscale of the Myers-Briggs Type Indicator and changes in pain and psychosocial variables were calculated by comparing participants’ recalled and current scores. Association between introversion/extraversion and other variables were assessed using linear regression. A parallel mediation was used to examine mediators of the association between introversion and change in pain interference. Higher introversion was associated with a decrease in pain interference after social distancing (Rho = − .194, p = .017). Parallel mediation analysis revealed that the relationship between introversion/extraversion and change in pain interference was mediated by changes in sleep disturbance and depression, such that higher introversion was associated with less isolation-induced sleep disruption and depression, and thereby less worsening of pain interference. These findings suggest that personality factors such as introversion/extraversion should be considered when personalizing treatment of chronic pain.