Cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD). However, CBT does not lead to a satisfying symptom reduction in a considerable number of patients with OCD. The identification of variables that predict insufficient treatment response could improve efficient treatment selection and inform the development of specific augmentative treatments. In the current study, we tested whether prediction of treatment response can be improved by including neurobiological markers during working memory (WM) performance. Forty-four patients with a primary OCD diagnosis participated in an n-back WM task with varying WM load while functional Magnetic Resonance Imaging (fMRI) was performed. Subsequently, all patients received CBT in an outpatient clinic. WM load-dependent modulation of the blood-oxygen-level-dependent (BOLD) signal in a bilateral cluster in inferior/superior parietal lobule predicted CBT response over and above clinical and sociodemographic variables (p < 0.05). Higher modulation was associated with larger relative symptom reduction. The results of the current study indicate that the ability of the WM system to flexibly adapt to changing task demands might be a useful indicator of CBT response in OCD. Possibly, this mechanism facilitates relearning processes during exposure-based CBT. However, findings need to be replicated in larger samples.