BACKGROUND: The current study aims to explore the efficacy of cognitive behavioral therapy (CBT) in normalizing social learning capabilities and its underlying neural processes among patients with MDD, in terms of enhancing learning towards positive social feedback, and reducing excessive learning towards negative social feedback. This study also explores the potential for learning impairments in social contexts as a biomarker to predict the effectiveness of CBT. METHODS: In a single-centre, single-arm, open-label trial, 60 outpatients with MDD will undergo 12 sessions of CBT in three months. Data collection of patients will be administered at baseline and at the endpoint of the treatment. Additionally, 60 heathy controls will be recruited as a comparative group to assess deviations from the normal functions in the patients with MDD before and after CBT. Data collection of the HC group will be administered at baseline. Data collection of the two groups comprises of demographic information, clinical assessments, psychological assessments, and behavioral experiments (i.e. the Door Game and the Trust Game) in conjuction with task-based function magnetic resonance imaging (fMRI) scanning. Data analysis comprises of an estimation of social learning capabilities by computational modeling, and identification of baseline abnormalities, treatment effects and endpoint abnormalities on social learning capabilities and its neural activities. DISCUSSION: This trial aims to assess the efficacy of CBT in normalizing social learning capabilities among patients with MDD by leveraging high ecological validity paradigms and computational modeling. This trial also contributes to understanding psychosocial biomarkers of CBT treatment effectiveness in reducing depressive symptoms. TRIAL REGISTRATION: ChiCTR2400094841 ( www.chictr.org.cn ; registration date: 12/29/2024) (retrospectively registered).