Background Blood biomarkers related to AF could be useful to detect silent AF and to develop stratified strategies for AF prevention. Previous studies identified markers that predict incident AF. However, it is difficult to differentiate whether biomarkers relate to underlying cardiovascular diseases, are generated by the atria in response to an AF episode, or both. We therefore measured a panel of blood biomarkers in patients without overt CVD with and without AF to investigate the association between biomarkers and atrial fibrillation (AF) in patients without overt cardiovascular disease (CVD). Methods Blood samples – drawn remote from an AF episode – of 60 patients with AF but without overt forms of CVD (idiopathic AF; iAF) were compared to 120 matched patients with sinus rhythm only. A novel antibody-based method for quantification of blood biomarkers (OlinkProseek Multiplex Cardiovascular) was used to compare 92 biomarkers between the two groups. Results N-terminal pro-B-type natriuretic peptide (NT-proBNP), Cathepsin L1, Endothelial cell-specific molecule 1, Cancer Antigen-125 (CA-125), Heat shock 27kDa protein, Galanin peptides, Proteinase-activated receptor 1, Stem cell factor, and CD40-ligand were all higher in iAF patients than in SR controls. Both NT-proBNP (OR1.55(1.07–2.25);p=0.022) and CA-125 (OR1.68(1.07–2.64);p=0.026) were independently associated with iAF. Conclusions This exploratory study, investigating over 90 cardiovascular blood biomarkers in patients without known CVD, identified one established biomarker for paroxysmal AF, NT-proBNP, and a novel marker, CA-125. CA-125 - previously unrelated to paroxysmal AF in an otherwise healthy population - may thus be a potential indicator of remote paroxysms of AF.