Introduction Delirium is a frequent and serious complication of cardiac surgery. However, the knowledge regarding pathogenesis of postoperative delirium is limited. Objectives To investigate whether increased levels of monocyte chemoattractant protein-1 (MCP-1) and hyper-sensitive C-Reactive Protein (hsCRP) are associated with postoperative delirium in cardiac surgery patients. Methods Patients were examined and screened for major depressive disorder (MDD) and cognitive impairment one day preoperatively, using the Mini International Neuropsychiatric Interview and The Mini-Mental State Examination Test. Blood samples were collected pre- and postoperatively for hsCRP and chemokine levels. Following surgical interventions, the Confusion Assessment Method for the Intensive Care Unit and the Memorial Delirium Assessment Scale with the cut-off score 10 were used to diagnose delirium. Results Postoperative delirium screening was found positive in 34% (61 of 177) of patients. Both, pre- and postoperative hsCRP, and preoperative MCP-1 levels were associated with postoperative delirium in univariate comparisons; p=0.001; p=0.0004; p < 0.001, respectively. However, according to a multivariate stepwise logistic regression analysis only MCP-1 concentration raised before surgery was independently associated with postoperative delirium, and related to advancing age of participants (Spearman’s Rank Correlation 0.192; p=0.0103). According to ROC analysis, the most optimal cut-off for MCP-1 concentration in predicting the development of delirium was 371.81 ng/ml with sensitivity of 77.0% and specificity of 58.6%. Conclusions The present study suggests that raised preoperative MCP-1 concentration is independently associated with delirium after cardiac surgery. Preoperative monitoring of pro-inflammatory markers combined with regular surveillance may be helpful in the prediction and early detection of postoperative delirium in this patient group.