In this study, several innate immunological adjuvants and related compounds were compared with respect to complement activation in serum and induction of cytokine release in whole blood samples using immunoassays. As found, simple lipids had no effect on the complement system or on cytokine release, whereas lipopolysaccharides induced prominent release of pro‐inflammatory cytokines (IL1β, TNF and IFNγ) without affecting the complement system, except for one, which activated the lectin pathway (LP). Moreover, saponin induced IL1β and MCP1 release and did not affect the complement system. The polysaccharide inulin exhausted the alternative pathway (AP) completely without affecting the LP and the classical pathway (CP), whereas zymosan exhausted the AP and had a major effect on the LP and CP as well. Peptidoglycans mainly affected the LP. Inulin, agarose and cellulose induced IL1β and MCP1 release, while dextran had no effect on cytokine secretion. Zymosan mainly induced IL1β release. The inorganic compound aluminium hydroxide, Al(OH)3, activated the complement system very efficiently (all three pathways) but only induced MCP1 release. Other compounds tested had minor/individual effects. Collectively, well‐known adjuvants, such as aluminum hydroxide, activated the complement system and/or induced pro‐inflammatory cytokine release. Since complement activation generates anaphylactic peptides, a simple definition of an (innate) immunological adjuvant can be inferred: it activates the (innate) immune system by complement activation and/or release of cytokines so as to attract cells of the adaptive immune system.