Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition with an onset typically during childhood. Evidence-based treatments include cognitive-behavioral therapy (CBT) and serotonin reuptake inhibitors. This study evaluates the extent that anxiety and OCD-related impairment may mediate symptom improvement during treatment. Data from a randomized treatment trial comparing CBT with placebo, CBT with standard sertraline dosing, and CBT with slowly titrated sertraline were evaluated to understand the extent to which anxiety and OCD-related impairment were systematically associated with improvement. Using correspondence analysis techniques, results generally supported that anxiety and OCD-related impairment mediated OCD symptom improvement. Anxiety and OCD-related impairment had attenuated effects on symptom improvement in those receiving CBT with slowly titrated sertraline, while both CBT with placebo and CBT with sertraline were comparable in efficacy. In addition to targeting OCD severity, treatment should also focus on anxiety and OCD-related impairment.