When growing fish in high-tech breeding systems, it is exposed to many stress factors. To reduce stress, we used spore forms of microorganisms — Bacillus subtilis and Bacillus licheniformis, possessing probiotic properties. Two groups were formed, a control group and an experimental group that received probiotic microorganisms with feed. The aim of the study was to evaluate the effectiveness of the use of microorganisms — Bacillus subtilis and Bacillus licheniformis to reduce stress in fishes. For this indicator points were selected — stress hormone cortisol and antioxidant defense enzymes. The research results showed that stress level assessed by cortisol in fishes fed with probiotic microorganisms is 2.8 times lower than in the control group. The use of micronucleus test to assess cytogenetic damage showed that against the probiotic microbiota background, the number of cells with fragmented nuclei decreases by 5.7 times. Antioxidant defense enzyme activity when using Bacillus subtilis and Bacillus licheniformis increased, indicating activation of the defense system against oxidative stress. The obtained results demonstrated the high efficiency of the use of spore forms Bacillus subtilis and Bacillus licheniformis when growing catfish in high-tech fish farming systems. The Russian Foundation for Basic Research has supported our study with the grant No. 18-016-00127.