In order to evaluate the effects of the interaction between different single novel proteins and feeding levels on largemouth bass (Micropterus salmoides), and to provide scientific guidance for the application of novel proteins and the corresponding optimal feeding strategy, five single protein diets (fishmeal (FM), Clostridium autoethanogenum protein (CAP), Tenebrio molitor (TM) Chlorella meal (ChM), cottonseed protein concentrate (CPC)) and three feeding levels (100 %, 80 % and 60 % satiety feeding) were designed to feed largemouth bass (weight: 2.96 +/- 0.08 g) for 8 weeks. Z-score combined with cluster analysis were used to analyze and compare the effects of different treatments on different indexes, such as growth performance, feed utilization, liver antioxidant capacity and immune response as well as lipid metabolism to draw a general picture of the relationship among all these massive biomarkers. The results showed that different novel protein sources and feeding levels had significant interactive effects on growth performance, feed utilization efficiency, body lipid and liver health of largemouth bass. Fish fed with ChM diet showed similar performance to that in FM group, implying its potential for complete replacement of fishmeal in largemouth bass. Fish fed with CAP, TM and CPC diets showed the worst performance by poor growth and feed utilization, enhanced stress, chronic inflammation, varies symptoms of histological changes in the liver and intestine, which demonstrated the adverse effects of the complete replacement of fishmeal by these three new proteins. As for feeding level, 100 % feeding level resulted in hypertrophy and fat accumulation in the liver of fish fed with FM and ChM diets and had risks of fatty liver. In addition, the TM and CPC group had the higher expression levels of inflammatory factors and the lower antioxidant enzymes activity at 100 % feeding level, and CAP group showed the higher expression levels of inflammatory factors at 60 % feeding level, which displayed that the interactions between CAP, TM, CPC diets and 100 % feeding level or 60 % feeding level may aggravate the occurrence of liver inflammation and oxidative damage of hepatocytes. Overall, 80 % feeding level had higher feed efficiency, protein efficiency, antioxidant enzyme and lysozyme activities, lower MDA content and lower gene