Objective to investigate the effects of hypoxia stress on gill, liver and kidney tissue structure and energy metabolism of grouper grouper backcross F2 generation (MLBCF2). Groupers were subjected to hypoxia stress with dissolved oxygen of 1.7 mg / L. tissue samples were taken at 0, 3, 6, 12, 24, 48, 72 h and reoxygenation for 3 h (75 h), and tissue sections were made. Blood samples were taken to measure and detect the values of serum aspartate aminotransferase (AST), alkaline phosphatase (ALP), serum triglycerides (TG), and serum total cholesterol (CHO). The gill lamellae were deformed in stages under hypoxia stress, with compensatory adaptation in the early stage, but the damage continued in the late stage and did not fully recover after reoxygenation; Vacuolization and sinusoidal dilatation occurred in the liver, and the injury was not completely repaired after reoxygenation; The kidney showed glomerular swelling, proximal tubule atrophy and inflammatory cell infiltration. Ast remained at a high level of 101.8 ± 16.7 U / L at 72 h, and returned to 43.62 ± 17.66 U / L after reoxygenation; ALP reached 301.98 ± 35.54 U / L at 72 h, and recovered to 278.53 ± 54.71 U / L after reoxygenation; Cho was maintained at 8.03 ± 1.39 mmol / L for 72 h and decreased to 5.59 ± 0.90 mmol / L after reoxygenation; TG increased slightly to 0.41 ± 0.06 mmol / L at 72 h, and returned to 0.53 ± 0.09 mmol / L after reoxygenation. These changes revealed that the liver maintained its function through lipid metabolism adjustment under hypoxia stress, but with tissue damage, although the metabolic indicators partially recovered after reoxygenation, the tissue damage was relatively delayed. This study focused on the physiological analysis of MLBCF2 hypoxia tolerance traits and the tissue recovery period after hypoxia exposure in high-density industrial aquaculture..