Study objective: To determine the prognostic value of the change in intraoperative BDNF (Brain-derived neurotrophic factor) levels during cardiac surgery with cardiopulmonary bypass (CPB) on early perioperative neurocognitive disorder (PND). Design: Prospective observational pilot study. Setting: The study was performed in the Medical Faculty Hospital, from January 2020 to August 2020. Patients: 45 adult patients undergoing elective coronary artery bypass surgery (CABG) with CPB. Interventions: None. Measurements: Cognitive function was evaluated 1 day before and 4 days after the surgery. Serum BDNF levels were measured at four time points (T1: after induction; T2: with aortic cross-clamp; T3: without aortic crossclamp; T4: 4 days after surgery) by enzyme-linked immunosorbent assay. Main results: The incidence of PND was 37.8% four days after surgery. Serum BDNF (T2 and T4) levels were significantly lower in PND group compared to non- PND group (p = 0.003 and p = 0.016, respectively). Moreover, lactate, rSO2 (regional cerebral oxygen saturation), aortic cross-clamp time, CPB duration, and the amount of blood transfusion differed between the groups. Logistic regression analysis identified serum BDNF-T2, age, cross-clamp time, and rSO2-T2 as independent risk factors for PND. Based on the ROC analysis, the area under curve (AUC) of BDNF-T2 concentration for prediction of PND was 0.759 with sensitivity of 71.4% and specificity of 64.7% (p < 0.01). Conclusion: Intraoperative BDNF serum levels may be a useful biomarker in predicting PND in patients undergoing CABG surgery. More comprehensive studies is needed in order to confirm the effect of decreasing intraoperative BDNF serum levels on the development of PND. Trial registration number: NCT04250935 www.clinicaltrials.gov.