Sustainable largemouth bass (Micropterus salmoides) culture development warrants a reduction of the inclusion levels of fish meal in feeds while maintaining optimal fish growth performance and nutrient utilization. The present study aimed to elucidate whether the low level fish meal diets affect largemouth bass growth and hepatic transcriptome profiles. Four isonitrogenous and isoenergetic diets containing 5% (FM5), 15% (FM15), 25% (FM25) and 35% (FM35) of fish meal were fed to fish individuals for 8 weeks in a recirculation system. The results showed no significant differences in specific growth rate and feed efficiency among treatment groups. Comparative analysis of hepatic transcriptome showed that the primarily identified genes involved in metabolic and immune pathways were modulated significantly, with the differentially expressed genes (DEGs) involved in lipid metabolism and transport (e.g. apoa1, fads2, fatp, fasn, elovl5 & elovl6) were mostly up-regulated in the fish fed with FM5 and FM15 diets, whereas numerous immune related genes (e.g. il1b, tlr2, ccr9, blnk & cd22) showed significant lower expression in both groups. In addition, several key antioxidant and stress related genes (sod1, gpx3, cat, gst & oxr1) showed elevated expression in the liver of fish fed with FM5 diet when compared to the FM35 diet. The present study suggested the potential impact of low fish meal diets on the metabolism and health of farmed juvenile largemouth bass, which will further contribute to optimal and sustainable feed formulations for the aquaculture industry of the species.