A ten-week feeding trial was carried out to investigate the effects of replacing fishmeal (FM) with soybean meal (SBM) and brewer's yeast (BY) on growth performance, blood parameters, oxidative stress and micromorphology of liver and intestines in brown bullhead (Ameiurus nebulosus L.). fish were fed nine feeds in which FM was replaced with 25%, 50%, 75% and 100% SBM (K1, K2, K3 and K4) and 17% + 8%, 42% + 8%, 67% + 8% and 92% + 8% of SBM/BY combination (K5, K6, K7, K8). Growth indices showed greater outcomes for the K2 group in comparison to all other groups. A decrease in plasma cholesterol and triglycerides concentrations was found after FM replacement. Activity of SOD was higher in groups K4, K7 and K8. The early inflammatory indications with abnormal vacuolization of lamina propria and basal epithelium were present in diets K4 and K8. Hepatocytes were irregular in shape with signs of inflammatory reaction in diet K8. A decreased perimeter of hepatocyte nuclei was detected in all experimental diets when compared with the control. This study demonstrates that the optimal replacement of FM with SBM/BY in brown bullhead diets contains up to 50% of FM replaced with SBM in order to obtain advantageous growth performance and adequate health condition. Aquaculture is one of the fastest growing industries in the food sector. The global supply of fish for human consumption has outpaced population growth in the past five decades-preliminary estimates suggest per capita intakes higher than 20 kg (20.2) 1 , double the level of the 1960s-that is mainly due to aquaculture growth, as the capture fisheries have stagnated in the last few decades. However, in 2010 aquaculture used 73% of global fishmeal production 2. Therefore, Hardy 3 argued that the industry would soon run out of sufficient quantities of fish oil and fishmeal (FM). As a result of increasing demand, limited supply and a dramatic increase in FM price, suitable alternative protein sources for fish feed have recently been intensively studied 4. In modern intensive aquaculture, feed formulations may account for more than 50% of the total production costs. Any reduction in feed costs with preserved health status of fish is bound to have a direct positive effect on the profitability of aquaculture production 5-7. Increasing feed efficiency, especially by improving the metabolic assimilation of dietary nutrients, is of the highest priority in contemporary animal production. The use of protein sources of plant origin as FM replacement in fish feed is a growing trend in the aquaculture industry. In this context, among commercially available plant protein alternatives, de-hulled and extracted SBM has one of the best amino acid balances 8 , except for the low level of methionine 9. It is widely available at competitive prices 3 , and is therefore one of the main dietary protein alternatives to FM in the feed of aquacultured species 10-13. Potential problems in soybean feeding exist due to the existence of antinutritional factors, which can cause malnutrition and lower p...