Objective: To examine whether or not acceptance of pain mediates the association between chronic pain and neuropsychological functioning. Methods: Ten community-dwelling individuals with chronic pain (lasting at least 1 year) were recruited on a voluntary basis in the Bay Area, California (7 women, mean age ¼ 56 years). Participants’ chronic pain had variable etiology, including fibromyalgia, arthritis, migraine headaches, sciatica, and neuropathy secondary to diabetes. Before and after treatment, participants completed a series of measures of acceptance of pain, experiential avoidance, coping profile, depression and anxiety, and somatization. Participants also completed a computer-based neuropsychological test of attention, memory, and processing speed (Immediate Post-Concussive Assessment and Cognitive Testing; ImPACT). Comparisons of hierarchical linear regressions were made to examine whether or not acceptance of pain mediates the association between chronic pain and neuropsychological functioning. Results: Acceptance of pain mediated the association between chronic pain and verbal memory (adjusted R2 change ¼ .34, t ¼ 21.23, ns), but not with visual memory (adjusted R2 change ¼ .39, t ¼ 22.58, p , .05). Conclusions: After participants underwent an acceptance-based treatment, increased pain severity was associated with decreased verbal and visual memory. Post-treatment, acceptance of pain mediated the association between chronic pain and verbal memory, but not with visual memory. The present study demonstrated the importance of acceptance-based treatment for individuals with chronic pain and subsequent deficits in neuropsychological functioning.