Low dissolved oxygen concentration is one of the main challenges in intensive aquaculture, compromising the physiological and metabolic processes of fish. This study evaluated the hematological, biochemical, and blood gas changes in juvenile Piaractus brachypomus subjected to hypoxia for different exposure periods, followed by reoxygenation. A total of 54 juveniles were distributed in a recirculating aquaculture system and initially maintained under normoxic conditions (5.59 mg L⁻¹). After 24 h of fasting, the animals were exposed to reduced dissolved oxygen concentrations (2 mg L⁻¹) for 1 h or 4 h. After exposure, the fish were maintained under reoxygenation conditions for up to 24 h, with blood samples collected immediately after hypoxic exposure (1 h and 4 h) and after reoxygenation (1 h, 6 h, and 24 h of recovery). The data were analyzed using two-way ANOVA and Tukey’s test, while comparisons with baseline values were performed using one-way ANOVA and Student’s t-test (P < 0.05). Hypoxic exposure did not cause mortality; however, it promoted important physiological adjustments. Hematocrit increased after 1 h of hypoxia and returned to normal levels during reoxygenation. The erythrocyte count decreased during hypoxia and increased during recovery, reaching baseline levels after 6 h. MCV increased during exposure and decreased after 24 h of recovery. Glucose decreased during recovery, whereas triglycerides and cholesterol increased under prolonged hypoxia. Lactate showed delayed accumulation during recovery after 4 h of hypoxia. Blood gases revealed acid–base changes, with variations in pH, bicarbonate, PCO₂, and oxygen saturation, as well as ionic changes during recovery. The results demonstrate the high adaptive capacity of P. brachypomus to acute hypoxia, activating rapid compensatory responses to maintain homeostasis.