The complement system mediates a number of essential biological functions that participate in host defense against infection, initiation of the inflammatory reaction, processing and clearance of immune complexes and regulation of the immune response. There are three pathways of complement activation: the classical pathway is initiated by immune complexes, the lectin pathway by surface bound mannan binding lectin and the alternative pathway by all the surfaces that are not specifically protected against it. Each complement pathway generates a C3 convertase, a serine protease that cleaves the central complement protein C3, and generates the major cleavage fragment C3b. C3b is an opsonin and part of one of the main convertases that drives the complement cascade. In the presence of complement regulatory molecules C3b may be further degraded sequentially to iC3b, C3c, C3dg and C3d. The disadvantage of most complement biomarkers is their short half-life, making reliable sample collection and measurements difficult. Unlike other C3 fragments, C3c does not bind to other structures like pathogens, cell surface (receptors) and other plasma proteins. Therefore, C3c is a stable complement biomarker which will appear in the fluid phase only, without interference of other C3 based products. The measurement of C3c provides evidence of (uncontrolled) complement activation and can be used as an indicator of an inflammatory state. The complement is a key element of the innate immune system. Inappropriate activation is pathologic and leads for example to various autoimmune diseases (e.g. HUS). There are also indications that C3 is associated with the cardiovascular system and Parkinson’s disease, making C3c a reliable and useful biomarker.The C3c ELISA, based on a antibody highly specific for a epitope exclusively on C3c, is a straightforward ELISA which can be used in diseases where complement activation is an element in an inflammatory response.