AbstractPost-operative atrial fibrillation (POAF) is the most common arrhythmia in the post-operative period after cardiac surgery. We aim to investigate the main clinical, local, and/or peripheral biochemical and molecular predictors for POAF in patients undergoing coronary and/or valve surgery. Between August 2020 and September 2022, consecutive patients undergoing cardiac surgery without previous history of AF were studied. Clinical variables, plasma, and biological tissues (epicardial and subcutaneous fat) were obtained before surgery. Pre-operative markers associated with inflammation, adiposity, atrial stretch, and fibrosis were analyzed on peripheral and local samples with multiplex assay and real-time PCR. Univariate and multivariate logistic regression analyses were performed in order to identify the main predictors for POAF. Patients were followed-up until hospital discharge. Out of 123 consecutive patients without prior AF, 43 (34.9%) developed POAF during hospitalization. The main predictors were cardiopulmonary bypass time (odds ratio (OR) 1.008 (95% confidence interval (CI), 1.002–1.013),p= 0.005), and plasma pre-operative orosomucoid levels (OR 1.008 (1.206–5.761). After studying differences regarding sex, orosomucoid was the best predictor for POAF in women (OR 2.639 (95% CI, 1.455–4.788),p= 0.027) but not in men. The results support the pre-operative inflammation pathway as a factor involved in the risk of POAF, mainly in women.