Abstract: An 8-week growth trial was conducted to investigate the effects of replacing dietary fishmeal with a novel protein blend and different feeding frequencies on growth performance, plasma biochemistry, intestinal morphology and antioxidant of largemouth bass (Micropterus salmonids) initial body weight of (14.23±0.07) g. Four non-food protein sources including cottonseed protein concentrate, Clostridium autoethanogenum protein, yellow mealworm meal and Chlorella meal were mixed at 8﹕5﹕3﹕4 to replace 0, 30%, 60% and 90% fishmeal (D1, D2, D3 and D4, respectively). The fish were fed at 1, 2 or 4 meals/d. The results showed that, at different feeding frequencies, specific growth rate (SGR) and protein retention efficiency (PRE) of largemouth bass in D4 group were significantly lower than those in D1, D2 and D3 groups, and feed conversion ratio (FCR) was significantly increased (P<0.05). Among the fish fed with different diets, those in the group fed 1 meal/d showed significantly lower SGR than the groups 2 and 4 meals/d groups (P<0.05). Furthermore, at different feeding frequencies, largemouth bass fed D4 diet demonstrated significantly lower plasma total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) contents levels compared to the D1 group, while alanine aminotransferase (ALT) levels were significantly higher (P<0.05). The plasma contents of aspartate aminotransferase (AST), glucose (GLU) and alkaline phosphatase (AKP) were significantly higher in the 1 meal/d group compared to the 2 and 4 meals/d groups (P<0.05), while the contents of total protein (TP) and albumin (ALB) were significantly lower than those of the other two groups (P<0.05). The D4 diet group showed significantly decreased crude lipid and plasma low density lipoprotein cholesterol (LDL-C) in whole body, while the moisture content was significantly higher (P<0.05). Moreover, the intestinal tissue of largemouth bass in D4 group had significantly higher malondialdehyde (MDA) levels compared to D1 group, while the activity of superoxide dismutase (SOD) was significantly lower than that in D2 group (P<0.05). The total antioxidant capacity (T-AOC) and catalase (CAT) activities in the group fed 2 meals/d were significantly higher than those in the group fed 1 meal/d (P<0.05). Histological results showed that the intestinal villus height, goblet cell number, muscle thickness and villus surface area of largemouth bass fed 2 meals/d were significantly higher than those fed 1 meal/d, while the intestinal crypt depth of largemouth bass fed 4 meals/d was significantly lower than that fed 1 meal/d (P<0.05). In conclusion, the 60% replacement of dietary fishmeal by the blend of four novel proteins fed at 2 meals/d could obtain better growth and feed utilization in largemouth bass.