ABSTRACT: Saline-alkaline stress, particularly sodium bicarbonate-induced alkaline stress, can cause tissue damage and oxidative stress in aquatic animals, thereby inhibiting their growth and even threatening their survival. This has become a key factor limiting the utilization of saline-alkaline water resources. In this study, Macrobrachium rosenbergii were selected as the research object to evaluate the physiological responses under acute (96 h) and chronic (56 d) alkaline stress at NaHCO3 concentrations of control (0.0 mmol/L), low (3.2 mmol/L, 30% LC50), and high (6.4 mmol/L, 60% LC50). Hepatopancreas samples were analyzed via histology, transmission electron microscopy, enzyme activity assays, and integrated transcriptomic and metabolomic analyses. The chronic exposure results showed activation of a coordinated energy network-evidenced by upregulated glycolysis (hk2, glut2 and enzymes HK, PFK, LDH), increased TCA intermediates (succinate, fumarate), and elevated oxidative phosphorylation metabolites, enhancing ATP production. Fatty acid metabolism exhibited a dose-dependent response: synthesis was upregulated under low stress (elevated fas, acsbgl2, and palmitic acid) likely for membrane remodeling, but suppressed under high stress. Prolonged exposure induced significant oxidative damage, evidenced by increased MDA, accumulated LysoPCs, and decreased SOD activity. Concurrently, a marked increase in autolysosomes indicated autophagy activation. Notably, these physiological disruptions were accompanied by a significant, dose-dependent decline in growth performance (FAW, WGR, SGR). These findings indicate that NaHCO3 stress induces integrated physiological responses in M. rosenbergii, including enhanced energy metabolism, oxidative injury, and autophagic activation, providing a reference for the development and utilization of saline-alkaline water resources.