Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, heightened chemosensory discharges of the carotid body (CB), which contributes to potentiate the ventilatory hypoxic response and elicits hypertension. We aimed to determine 1) whether the persistence of cardiorespiratory alterations found in long-term CIH depends on the inputs from the CB and 2) in what extension the activation of glial cells and neuroinflammation in the caudal region of the nucleus of the solitary tract (NTS) require functional CB chemosensory activity. To evaluate these hypotheses, we exposed male mice to CIH for 60 days. At 50 days of CIH, CBs were denervated and animals were kept in CIH for 10 additional days. At the end of the experiments, we measured arterial blood pressure, breathing regularity, and hypoxic ventilatory response (HVR) and assessed astrocyte and microglia cell activation. Compared to sham treatment, CIH induced hypertension [mean arterial blood pressure (MABP): 83.47 ± 1.39 vs. 95.00 ± 2.18 mmHg] and disordered breathing [irregularity score (IS): 7.77 ± 0.49 vs. 12.56 ± 1.66], increased the HVR [1.69 ± 0.17 vs. 4.31 ± 0.87 change in minute ventilation (ΔVE)/min], and produced an early transient activation of astrocytes followed by a late and persistent activation of microglia in the NTS. In addition, CIH increased IL-1β, IL-6, and TNF-α levels in the NTS. Bilateral CB denervation after 50 days of CIH results in the restoration of normal glial cell activation in the NTS, lower levels of IL-6 and TNF-α, and reductions in arterial blood pressure (83.47 ± 1.38 mmHg) and HVR (1.63 ± 0.43 ΔVE/min). The present results suggest that CB inputs to the NTS during long-term CIH contribute to maintain the cardiorespiratory alterations and the formation of a neuroinflammatory niche at the NTS by modifying glial cell activity.