Decreased plasma glucose concentration elicits a complex neuroendocrine response that prevents or rapidly corrects hypoglycemia as required to preserve brain function; however, where and how low glucose is sensed is unknown. Here we show that low glucose increases secretion from glomus cells in the carotid bodies, sensory organs whose stimulation by hypoxia produces sympathetic activation, by a process that depends on extracellular Ca2+ influx and is paralleled by inhibition of voltage-gated K+ channels. We propose a new glucose-sensing role for the carotid body glomus cell that serves to integrate information about blood glucose and O2 levels and to activate counterregulatory responses.