Flow velocity is a critical environmental factor influencing the growth, energy metabolism, and physiological health of aquaculture species. This study investigated the physiological and molecular responses of spotted sea bass (Lateolabrax maculatus) under experimental conditions simulating flow velocities typical of land-based recirculating aquaculture systems (RAS) and deep-sea cage systems. High flow velocities (HFV, 0.35–0.65 body lengths per second [BL/s]) enhanced growth performance compared to low flow velocity (LFV, 2.28–2.85 BL/s) conditions. Histological analysis revealed reduced hepatic lipid accumulation under HFV, while LFV promoted lipid storage. Serum analyses showed elevated antioxidant enzyme activity in the LFV group but higher oxidative stress markers in the HFV group. Transcriptomic profiling identified foxo3 as a key regulatory hub orchestrating metabolic and oxidative stress adaptations. Genes associated with oxidative damage repair, lipid catabolism, and glucose metabolism were significantly enriched under hydrodynamic stress. Enrichment of the FoxO signaling pathway highlighted its central role in mediating oxidative stress mitigation and energy mobilization. These findings demonstrate the dual effects of flow velocity, where higher velocities promote growth and metabolic activity at the cost of oxidative stress, and lower velocities conserve energy while maintaining oxidative stability. Tailored flow velocity conditions can optimize fish welfare and productivity across aquaculture systems. Future studies should investigate the systemic effects of hydrodynamic stress using multi-omics approaches to advance sustainable aquaculture practices.