Abstract: Symphysodon aequifasciatus has a unique parental rearing behavior. In the previous study, two C-type lectins (CTLs) were found to be highly expressed in the skin of parent fish, but with different expression patterns. In order to investigate the difference in the potential immune functions of the specific CTLs, we cloned two CTL genes (SaCD302 and SaMBL), then simulated and analyzed their immune esponse patterns under pathological infection. The results show that the ORF region ofSaCD302 and SaMBL were 741 and 795 bp in length, encoding 246 and 264 amino acids (aa), respectively. The SaCD302 sequence contained a signal peptide (aa 1–29), a C-type lectin-like domain (CTLD) (aa 32–169) and a transmembrane domain (aa 184–206). Two low complexity regions (aa 32–92 and aa 104–121) and a CTLD (aa 137–263) were expressed in SaMBL sequence. Moreover, SaCD302 and SaMBL shared the highest similarity with that of Archocentrus centrarchus. SaCD302 was highly expressed in the head kidney, followed by the liver and gill. Compared with the intestine, liver, spleen and gonads, the skin had the higher expression of SaMBL. After Aeromonas hydrophila infection, SaCD302 expression was significantly upregulated in the spleen, head kidney, intestine and skin, whileSaMBL was only upregulated in the head kidney, intestine and skin, and these two genes were expressed in different temporal manners, indicating that they might play different roles in the immune defense of S. aequifasciatus.