Background: Chronic rhinosinusitis (CRS) is characterized by significant accumulation and thickening of mucus in the sinonasal cavities. One contributor of aberrant mucus production and impaired mucociliary clearance (MCC) is altered function of the sinonasal submucosal glands (SMGs), yet contributions of SMGs to upper airway disease initiation and progression remain unknown. The objective of this study was to characterize the morphology and secretory cell identities of the nasal septum SMGs in both healthy and CRS adults.Methods: Biopsies from adult participants with CRS without nasal polyps (CRSsNP, n = 4), CRS with nasal polyps (CRSwNP, n = 8), and non-CRS controls (n = 14) were collected from the posterior septum. Glandular morphology and mucus markers were investigated using histological techniques and highresolution confocal microscopy. Results: Analysis revealed a significant decrease in gland density in the posterior septum of CRSsNP (28% ± 6.15%) and CRSwNP (23% ± 3.09%) compared to control participants (53% ± 1.59%, p < 0.0001). Further analysis of the CRS SMG secretory function revealed an overall decrease in Mucin 5B+ gland mucus being produced. Dilated and cystic ductal structures filled with inspissated mucus were also common to CRS glands. Conclusion:Here, we describe a significant alteration in SMG structure and function in the adult CRS posterior septum suggesting reduced gland contribution to MCC. The SMGs of both the nose and sinuses may represent targets for future therapeutic approaches.