Background Serum level of interleukin 6 (IL-6) is known to be associated with postoperative delirium. However, no consensus has emerged on the postoperative time point at which IL-6 level may predict postoperative delirium after coronary artery bypass graft surgery. Objectives To compare trends in IL-6 levels in patients with and without postoperative delirium and to examine the relationship between IL-6 levels at different times and postoperative delirium after coronary artery bypass graft. Methods A prospective cohort study of patients who underwent their first elective isolated coronary artery bypass graft between November 2013 and August 2015 at a cardiac intensive care unit in Beijing, China. Concentrations of IL-6 were measured before the operation and at the 6th, 12th, and 18th postoperative hours. Participants were assessed for postoperative delirium twice daily for 5 days. Univariate and multivariate logistic regression analyses were done to determine associations between IL-6 levels at different time points, postoperative changes in IL-6 levels, and the occurrence of postoperative delirium. Results Postoperative delirium was diagnosed in 85 of 266 patients (32%). Levels of IL-6 were significantly higher in patients with postoperative delirium than in patients without it at the 6th, 12th, and 18th postoperative hours ( P = .03, .004, and .001, respectively). Change in IL-6 level (odds ratio, 2.97; 95% CI, 1.20-7.31; P = .02) and IL-6 level of 583 pg/mL or higher at the 18th postoperative hour (odds ratio, 5.20; 95% CI, 1.84-14.70; P = .002) were associated with higher incidence of postoperative delirium. Conclusion Interleukin 6 level (≥ 583 pg/mL) at the 18th postoperative hour may serve as a potent predictor of postoperative delirium in coronary artery bypass graft patients.