Postoperative delirium is a common complication in older patients. Changes in adipokine levels are associated with advanced stages of dementia and aging. However, the role of adipokines in the development of postoperative delirium has not been fully investigated. In this study, we examined the association between delirium and adipokines including, adiponectin, resistin, and leptin after surgery. We conducted a post hoc analysis of 117 patients who participated in a prospective observational study of delirium in patients undergoing cancer surgery. The patients were clinically assessed for delirium within the first 5 days after surgery. Serum levels of adipokines such as adiponectin, resistin, and leptin as well as related inflammatory markers were measured on postoperative day 3. Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Serum levels of adiponectin on postoperative day 3 were significantly decreased in patients with delirium compared with those without delirium (8.615 [8.005–11.306] vs. 11.306 [8.465–11.306], P = 0.0031) whereas levels of resistin were increased (10.960 [10.742–11.050] vs. 10.393 [9.794–11.126], P = 0.0018). Serum levels of adiponectin were associated with delirium (adjusted odds ratio [aOR], 0.673; 95% confidence interval [CI], 0.514−0.882; P = 0.0030) and the detection of phosphorylated neurofilament heavy subunit (aOR, 0.666; 95% CI, 0.494−0.900; P = 0.0057). Serum adiponectin levels were associated with delirium and the presence of phosphorylated neurofilament heavy subunit in serum. Therefore, adiponectin might be one of the useful biomarkers of postoperative delirium.