A biofloc technology system is a complicated microbial ecosystem that requires some time in culture to stabilize inorganic nitrogen assimilation and the quality biofloc formation. The establishment of a biofloc technology system generally results in the accumulation of ammonia or nitrite. The growth and immune enzymes of the Genetically Improved Farmed Tilapia (GIFT) strain of were examined during the initial establishment of a biofloc technology system. A total of 600 tilapia with an average weight of (24.17± 2.49) g ( ±SD) were raised for 30 days, half in an indoor recirculating aquaculture system (control group) and half in a biofloc technology system (treatment group). Sodium acetate was added to the biofloc technology system at rate of 75% feed to maintain an optimum CN ratio of heterotrophic bacteria. The two groups were fed commercial feed at a daily rate of 2% of total fish body weight. The daily feeding rate was adjusted every 10 days based on the weight of a fish sample. Total suspended solids were maintained at roughly 500 mg/L in the control group. Both systems were maintained at a water temperature of 24–26 with dissolved oxygen (DO) concentrations over 6 mg/L and a pH of 7.0–7.5, which was adjusted using NaHCO₃. A simulated natural photoperiod (12L12D) was used. During establishment of the biofloc technology system, concentrations of ammonia and nitrite rapidly spiked and then decreased, reaching peak concentrations of (60.98± ±SD), respectively. Nitrate concentrations stayed at relatively low levels of 1–15 mg/L. In contrast, nitrate levels rose markedly in the control group, ranging from (73.03±3.29) mg/L to (152.44±1.79) mg/L. Concentrations of ammonia and nitrite, however, were relatively stable and maintained relatively low levels of 5 and 0–3 mg/L, respectively. There was no significant difference between treatments in the activities of alkaline phosphatase, lysozyme, or total superoxide dismutase of the hepatopancreas, head kidneys, and serum; however, total superoxide dismutase and lysozyme activity in the hepatopancreas were significantly lower in the treatment group than in the control. In contrast, the specific growth rate, hepatosomatic somatic index, fullness, and protein efficiency ratio of the treatment group were significantly higher than that of the control group (<0.05), while the feeding rate in the treatment group was lower than the control (>0.05). Relative to the control, the feed conversion ratio in the experimental group was significantly lower (<0.05). Survival was 100% for both groups, indicating no significant stress reaction to biofloc establishment. Moreover, tilapia grew at faster rates in the biofloc system than the recirculating system.