Both posttraumatic stress disorder (PTSD) and depression are highly comorbid with chronic pain and have deleterious effects on pain and treatment outcomes, but the nature of the relationships among chronic pain, PTSD, and depression has not been fully elucidated. This study examined 250 Veterans Affairs primary care patients with moderate to severe chronic musculoskeletal pain who participated in a randomized controlled pain treatment trial. Baseline data were analyzed to examine the independent associations of PTSD and major depression with multiple domains of pain, psychological status, quality of life, and disability. PTSD was strongly associated with these variables and in multivariate models, PTSD and major depression each had strong independent associations with these domains. PTSD demonstrated similar relationships as major depression with psychological, quality of life, and disability outcomes and significant but somewhat smaller associations with pain. Because PTSD and major depression have independent negative associations with pain, psychological status, quality of life, and disability, it is important for clinicians to recognize and treat both mental disorders in patients with chronic pain.