The complement system plays a key role in homeostasis and defense against pathogens. The antimicrobial activity of serum against Gram-negative bacteria is usually attributed to the action of the membrane attack complex. However, there is increasing evidence that some other components of the complement system and the products of its activation are also capable of direct killing of both Gram-negative and Gram-positive bacteria. In the course of complement activation, anaphylatoxins C3a, C4a, C5a are produced, which, in addition to their main function, can exhibit a bactericidal effect and disrupt the bacterial membrane. Recent studies have shown that in fish, complement factors D, I, as well as a Ba fragment of factor B, are able to neutralize pathogens. The triggering and amplification of complement usually occurs on the surface of pathogen cells, so the local production of antimicrobial components can potentially make a significant contribution to their elimination. The aim of this review is to outline the role of individual complement members in the elimination of pathogens through direct antibiotic action. The problem of antimicrobial protection in the context of therapeutic complement inhibition is considered.