As the cheapest energy source, carbohydrates are used in fish feeds to improve physical quality and reduce catabolism of proteins and lipids. The liver is the primary organ for metabolism and is also an important site of immune regulation. Here, we investigated the effect of different dietary carbohydrate levels on growth and health by evaluating the liver transcriptome of Epinephelus akaara. In this study, E. akaara juveniles were fed diets containing few (0% corn starch), moderate (18% corn starch), and high (30% corn starch) levels of dietary carbohydrate. After an 8-week feeding trial, E. akaara fed 30% dietary carbohydrates exhibited poor growth performance compared with those fed 0% and 18% dietary carbohydrates (P > 0.05). Genes related to the immune system, including IL8, TLR9, CXCR4, CCL4, and NFκB inhibitor alpha, were over-expressed in E. akaara fed the highest level of carbohydrate (30%). This general over-expression could indicate activation of inflammatory processes in the liver. The liver transcriptome data of E. akaara reported here indicate that high carbohydrate level of diet can lead to poor growth and inflammatory immune response in E. akaara.