The aim of the present study was to investigate the effects of dietary vitamin E (vit E) and selenium nanoparticles (nanoSe) on liver proteome profile of rainbow trout under high density condition. To correlate the proteome modifications with physiological aspects, growth, serum metabolites (cortisol, glucose, lactate, ALT, AST, and ALP), and liver antioxidant-related parameters (SOD, GPx, CAT, and MDA) were also examined. A total of 1275 fish (average weight of 42.6±2.3g) were stocked into 12 tanks at a density of 80kgm. The fish were divided into four groups according to diet: control (basal diet), vit E (500mgkg vit E-supplemented diet), nanoSe (1mgkg nanoSe-supplemented diet), and combination (500mgkg vit E and 1mgkg nanoSe-supplemented diet). After 60days, the best performance and health status of fish were observed in vit E and combination groups. Supplementation with nanoSe had no significant effects on growth performance. In addition, we compared liver proteome profiles of fish fed with a basal diet (control) and diets supplemented with vit E or nanoSe. Among the identified proteins, GRP78, ATPsyn-d, and HSP70 had an increased abundance in the vit E group, while HPPD and GAPDH showed a decreased abundance. In response to nanoSe supplementation, the expression of MDH, FAA, FBPA, TPI, GRHPR, GNMT, FDH, and Enol was increased. The proteomic data indicate that vit E or nanoSe supplementation can alter the expression of proteins involved in metabolic status of rainbow trout reared under high rearing density.