Our recent study demonstrated that diet with blend oil (named BO1) as lipid, which is designed on the base of essential fatty acid requirement of Trachinotus ovatus, achieved good performance. Here, to confirm its effect and investigate the mechanism, three isonitrogenous (45%) and isolipidic (13%) diets (D1-D3) only differing in dietary lipids, which were, respectively, fish oil (FO), BO1, and blend oil 2 (BO2) consisting of FO and soybean oil at 2 : 3, were formulated and used to feed the T. ovatus juveniles (average initial weight: 7.65 g) for 9 weeks. The results showed that the weight gain rate of fish fed D2 was higher than that of fish fed D3 (
P
<
0.05
) and had no significant difference from that of fish fed D1 (
P
>
0.05
). Correspondingly, compared with the D3 group, fish of the D2 group exhibited better oxidative stress parameters such as lower serum malondialdehyde content and inflammatory indexes in the liver such as the lower expression level of genes encoding four interleukin proteins and tumor necrosis factor α, as well as higher hepatic immune-related metabolites such as valine, gamma-aminobutyric acid, pyrrole-2-carboxylic acid, tyramine, l-targinine, p-synephrine, and butyric acid (
P
<
0.05
). Furthermore, the intestinal probiotic (Bacillus) proportion was significantly higher, while the pathogenic bacteria (Mycoplasma) proportion was significantly lower in the D2 group than that in the D3 group (
P
<
0.05
). The main differential fatty acids of diet D2 were close to those of D1, while the levels of linoleic acid and n-6 PUFA, as well as the ratio of DHA/EPA of D3, were higher than those of D1 and D2. These results indicated that the better performance of D2 such as enhancing growth, reducing oxidative stress, and improving immune responses and intestinal microbial communities in T. ovatus may be mainly due to the good fatty acid composition of BO1, which indicated the importance of fatty acid precision nutrition.