Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region's role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry and CBTp responsiveness and emotional decision-making as measured by the Iowa Gambling Task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6–8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging and performed the IGT. Patients’ symptoms were assessed before and after therapy. Pre-therapy OFC GMV, measured using a region-of-interest approach, and IGT performance, measured as overall learning, attention to reward, memory for past outcomes and choice consistency, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV was correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC's function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness.