Background The incidence and risk factors of postoperative neurocognitive disorder (PND) following coronary artery bypass grafting (CABG) is still controversial. Exploring an effective and reliable predictor of PND is essential to the prevention of PND. This prospective observational study aimed to find the incidence rate as well as possible risk factors of PND in CABG.Methods Patients who underwent CABG were included. A battery of neuropsychological tests was performed preoperatively and 7 days after surgery. We used the Z score to analyze and comprehensively evaluate PND. The clinical characteristics of the patients were recorded. The levels of TNF-α, IL-1 (interleukin-1), IL-6 (interleukin-6), S100β, MDA (malondialdehyde) and T-AOC (total antioxidant capacity) were measured at different time points.Results A total of 82 patients were enrolled in the study. The incidence of PND was 25.6% 7 days after surgery. Patients were divided into the control group (N = 61) and the PND group (N = 21). The average age of patients in the PND group was 68.1 years, which was 64 years in the control group (P < 0.05). The average years of education in the PND group were significantly shorter than those in the control group (P < 0.05). The serum levels of IL-6, MDA, Il-1, and S100β in the PND group were significantly lower than those in the control group 1 day after surgery, and the T-AOC level was higher than that in the control group (P < 0.05) 1 day after surgery. The concentration of S100β in the PND group significantly higher than that in the control group 3 days after surgery (P < 0.05). Age, years of education, IL6, TAOC, MDA, IL1, and S100B were included in the multiple regression to search for risk factors of PND. The results showed that higher age (95%CI = 0.776–0.984, P = 0.026), lower years of education (95%CI = 1.006–1.736, P = 0.045) and higher MDA level (95%CI = 0.304–0.964, P = 0.037) were risk factors for PND.Conclusions Older age, lower educational level and higher MDA might be risk factors for PND 7 days after surgery. More researches in the future on this field needs to be conducted to prevent PND effectively and timely.Trail registration: The trail has been registered to the Chinese Clinical Trail Registry (ID: ChiCTR1800015606) on April 11, 2018.