Ficolin-1 (M-Ficolin) is a pattern recognition molecule of the complement system that is expressed by myeloid cells and type II alveolar epithelial cells. Ficolin-1 has been shown to localize in the secretory granules of these cells and attached to cell surfaces, but whether Ficolin-1 exists a soluble molecule in the extracellular environment or in plasma is unknown. In this study we explored the possibility that Ficolin-1 may be secreted from monocytes, macrophages or immature dendritic cells and may exist in human plasma. Expression of Ficolin-1 was analyzed using real-time quantitative PCR and SDS-PAGE/western blot. Secretion of Ficolin-1 was investigated in cells and plasma from healthy donors through affinity purification using N-acetyl-d-glucosamine-agarose beads and ELISA. Ficolin-1 was found differentially expressed and synthesised by monocytes, macrophages and immature dendritic cells. Notably monocytes and macrophages, but not immature dendritic cells are able to secrete Ficolin-1 into the extracellular environment. Moreover, Ficolin-1 was detected in human plasma from healthy donors with a median concentration of 60.5 ng/ml ranging from 45.7 to 100.4 ng/ml. We show that Ficolin-1 is secreted into the extracellular environment from human monocytes/macrophages, but not immature dendritic cells. Importantly, these results demonstrate that Ficolin-1 exists in human plasma and serum under normal conditions, hereby revising the general assumption that Ficolin-1 is solely a cellular associated protein.