Recent work has shown that the carotid chemoreceptor (CC) contributes to sympathetic control of cardiovascular function during exercise, despite no evidence of increased circulating CC stimuli, suggesting enhanced CC activity/sensitivity. As interactions between metaboreceptors and chemoreceptors have been previously observed, the purpose of this study was to isolate the metaboreflex while acutely stimulating or inhibiting the CC to determine if the metaboreflex increased CC activity/sensitivity. Fourteen young healthy men (Height: 177.0±2.1 cm, Weight: 85.8±5.5 kg, Age: 24.6±1.1) performed three trials of 40 % maximal voluntary contraction handgrip for 2min, followed by 3min of post-exercise circulatory occlusion (PECO) to stimulate the metaboreflex. In random order, subjects either breathed room air, hypoxia (target SpO₂=85 %), or hyperoxia (FIO₂=1.0) during the PECO in order to modulate the chemoreflex. Following these trials, a resting hypoxia trial was conducted without handgrip or PECO. Ventilation (VE), heart rate (HR), blood pressure and muscle sympathetic nervous activity (MSNA) data were continuously obtained. Relative to normoxic PECO, inhibition of the CC during hyperoxic PECO resulted in lower MSNA (p=0.038) and HR (p=0.021). Relative to normoxic PECO, stimulation of the CC during hypoxic PECO resulted in higher HR (p<0.001) and VE (p<0.001). The ventilatory and MSNA responses to hypoxic PECO were not greater than the sum of the responses to hypoxia and PECO individually, indicating that the CC are not sensitized during metaboreflex activation. These results demonstrate that stimulation of the metaboreflex activates, but does not sensitize the CC, and help explain the enhanced CC activity with exercise.