Cognitive decline occurs frequently after cardiac surgery and it may lead to patient morbidity. The purpose of this study is to focus on the static incidence of neuro-psychiatric impairment associated with altered inflammatory biomarkers in the cerebro-spinal fluid (CSF) that may provide an insight into the mechanisms of acute peri-operative cognitive disturbances related to heart surgery. Immuno-assays were used to evaluate concentrations of several cytokines in CSF of patients undergoing either off-pump coronary artery bypass grafting (OP-CABG) or major non-cardiac surgeries. Inter-group analysis showed no differences in baseline cytokine abundance. Levels of IL-8 have markedly increased both after OP-CABG and major non-cardiac surgeries (34.59+/-7.15 vs. 99.45+/-6.35, and 27.44+/-7.17 vs. 66.63+/-15.18). Rantes showed significantly greater quantity in CSF of the non-cardiac group after surgery (8.71+/-3.37 vs. 114.56+/-65.42), whereas it became somewhat less abundant in the post-operative period but statistically unchanged in the OP-CABG cohort (19.87+/-15.71 vs. 9.37+/-3.65). IP-10 and MCP-1 did not show significant changes in their concentrations in either patient population (OP-CABG: 254.41+/-160.01 vs. 224.55+/-214.39, and 140.37+/-40.98 vs. 147.16+/-37.98; non-cardiac: 274.99+/-219.44 vs. 395.09+/-468.30, and 126.56+/-31.24 vs. 124.41+/-49.89, respectively). These findings suggest that cardiac surgery provokes alterations in the levels of various cytokines in the CSF, and the OP-CABG induced changes in biomarker profile differs from that seen after major non-cardiac surgeries. This, along with other biomarkers, may offer an explanation for relationships between the pronounced incidence of cognitive impairment after heart operations.