A six-week study was conducted to assess the effect of dietary fish meal (FM) replacement with Sargassum ilicifolium meal (SIM) at four substitution levels including 0 (control), 3% (S3), 6% (S6) and 9% (S9) on performance of Asian sea bass (Lates calcarifer) juveniles (initial mean body weight of 29.0 ± 1.0 g). Growth performance pronouncedly increased in SIM-supplemented groups compared to the control (P < 0.05). Fish fed on the S6 diet had higher pancreatic digestive enzyme activities than other treatments. Supplementing diet with SIM remarkably enhanced red blood cell count compared to the control. Moreover, fish in the control and S3 groups had higher lymphocyte, but lower neutrophil percentages than the S6 and S9 treatments (P < 0.05). The greatest and the least amounts of the total protein and total immunoglobulins (Ig) in serum were found in the S6 and the control, respectively. The amount of alternative complement pathway activity in the serum of fish in the S9 group was higher than the other groups, whereas higher serum lysozyme activity was found in the S6 and S9 treatments compared to those in the control and S3 groups (P < 0.05). Total Ig content of the skin mucus in the S6 and S9 groups was higher than the control. The greatest and the least mucosal lysozyme activates were found in the S6 and control, respectively (P < 0.05). The liver superoxide dismutase activity in the S6 and S9 groups was higher than the other treatments (P < 0.05). The insulin like growth factor-1 mRNA transcript abundance levels in the liver were greatest and the least in fish fed on the S9 and control, respectively. The expression of lysozyme gene, as indicated by an abundance of mRNA transcript for lysozyme, in the liver was higher in the S6 and S9 groups than the other groups (P < 0.05). Furthermore, fish fed the SIM incorporated diets had higher interlukine-1? mRNA transcript abundance in the liver compared to the control (P < 0.05). Overall, according to the findings of this