In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65 years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL-8, and S100B were assayed in repeated blood samples. 120 patients (mean age 84 years, 62 patients with delirium) were included. Highest levels of IL-8 (27.1, 95% Confidence Interval (CI): 13.6-53.1 pg/ml) and cortisol (666, 95% CI: 475-859 nmol/L) were before delirium, but of IL-6 (84.3, 95% CI: 46.5-151.4 pg/mL) and S100B (0.18, 95% CI: 0.12-0.24 microgram/L) during delirium. In multivariable analysis cortisol, LogIL-6, and LogS100B were significantly associated with delirium, but adjusted for pre-existing cognitive impairment, only LogS100B remained significantly associated. Cortisol, IL-6 and S100B may have a role in the pathogenesis of delirium, but S100B is the strongest independent marker. (Contains 3 tables and 1 figure.)