Florida Bay’s shallow seagrass beds experience daily diurnal fluctuations in environmental oxygen, leading to hypoxic episodes (PO2 < 2 mg∙L-1, 4.6 kPa) that have increased in recent decades. To survive, the native Gulf toadfish can employ a suite of adaptive cardiorespiratory and metabolic adjustments. Previous work has demonstrated that toadfish reduce heart rate (HF) and increase ventilatory amplitude during moderate hypoxia (PO2 ~2-4 kPa for 20 min). Toadfish also have a regulation index of 0.5, suggesting that they use strategies other than maintaining oxygen consumption to tolerate hypoxia. The objective of this study was to characterize the acute response of Gulf toadfish to severe hypoxia (< 2 kPa). We hypothesized that Gulf toadfish would respond to severe hypoxia by reducing energy expenditure while switching to anaerobic metabolism. Cannulated adult toadfish (0.062 kg ± 0.003; n=29) were exposed to either control conditions (normoxia for 4 h) or hypoxia (PO2 ~ 0.44 kPa for 3 h followed by 1 h recovery). Cardiovascular and ventilatory parameters were monitored and blood samples were taken from both groups at t = 0, 1.5, and 4 h, and analyzed for pH, glucose, lactate, and other endpoints. Hypoxia-exposed fish experienced a ~72% decrease in HF and a ~25% decrease in VF during hypoxia exposure. Moreover, plasma glucose concentrations increased 5-fold, and plasma lactate concentrations increased 10-fold while pH decreased by 2.7% during hypoxia exposure. Our findings support our hypothesis that toadfish survive hypoxia by reducing energy expenditure and switching to anaerobic metabolism.