AIM OF THE STUDY: In patients undergoing cardiac surgery, preoperative depressive and anxiety symptoms and increased postoperative C-reactive protein (CRP) levels have been associated with adverse outcomes. We tested the hypothesis that preoperative depressive and anxiety symptoms predict elevated in-hospital CRP levels after cardiac surgery. METHODS: The study participants were 96 consecutive patients (mean age [SD], 67.6 [10.3] years, 78.1% men) from a single cardiac surgery centre who underwent either isolated coronary artery bypass grafting (CABG) (n = 34), isolated valve surgery (n = 29), combined procedures (including different combinations of CABG, valve surgery, aortic surgery, and others) (n = 30), or other cardiac surgical procedures (n = 3). Participants self-rated depressive and anxiety symptoms using the Patient Health Questionnaire (PHQ-9) and the General Anxiety Disorder (GAD-7) questionnaire before undergoing elective surgery. CRP levels were measured every 24 h up to 10 days post-surgery. Linear mixed (random effects) regression analysis examined the association between preoperative depressive and anxiety symptoms and CRP levels over time, adjusting for pre-surgery CRP levels, demographics, cardiovascular risk factors, medications, and surgery-related variables. RESULTS: Before surgery, 32.2% of patients had clinically relevant depressive symptoms (PHQ-9 score ≥5) and 32.2% of patients had clinically relevant anxiety symptoms (GAD-7 score ≥5). More severe depressive symptoms (estimate [95% CI]: 0.081 [0.023, 0.139], p = 0.007) and more severe anxiety symptoms (0.059 [0.005, 0.113], p = 0.032) predicted CRP levels over 10 days, independent of covariates. Furthermore, CRP levels were higher in patients with than in those without clinically relevant depressive symptoms (0.697 [0.204, 1.191], p = 0.006) and were predicted by both more severe somatic (0.132 [0.035, 0.229], p = 0.008) and cognitive (0.128 [0.014, 0.242], p = 0.029) depressive symptoms. CONCLUSIONS: Preoperative depressive and anxiety symptoms were independent predictors of elevated CRP levels up to 10 days post-surgery. Such a mechanism may help explain the increased morbidity and mortality risk in patients with depression and anxiety who undergo cardiac surgery.