Complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. Complement regulators are crucial to prevent the injudicious production of these mediators and potential injury to self tissues. Here, we identified the complement factor H (CFH) and its related gene 2 (CFHR2) homologs from large yellow croaker (Larimichthys crocea), named LcCfh and LcCfhr2, respectively. The deduced LcCfh and LcCfhr2 proteins shared significant structural similarities and identified codes for a polypeptide consisting of various numbers of highly conserved SCR domains. LcCfh, LcCfhr1 and LcCfhr2 genes were detected in all examined tissues with predominantly expressions in liver, spleen and kidney, and their expressions all increased upon Vibrio alginolyticus challenge. In vitro assays showed that recombinant LcCfh was likely to act as a cofactor of CFI and played a negative regulation role in complement system, when recombinant LcCfhr2 seemed to play mechanisms independent of the activity of CFH. Both recombinant LcCfh and LcCfhr2 took participate in inflammatory reaction despite of the inequal ability to mediate pro-inflammation response. These data provide a new insight into the functional activities of teleost complement system.