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Respiratory infections caused by the human fungal pathogens, and , are a major cause of mortality for immunocompromised patients. Exposure to these pathogens occurs through inhalation, although the role of the respiratory epithelium in disease pathogenesis has not been defined. Employing a primary human airway epithelial model, we demonstrate that fungal melanins potently block the post-translational secretion of CXCL1 and CXCL8 independent of transcription or the requirement of melanin to be phagocytosed, leading to a significant reduction of neutrophils to the apical airway both and . -derived melanin, a major constituent of the fungal cell wall, has far-reaching effects, dampening airway epithelial chemokine production in response to fungi, bacteria, and exogenous cytokines. Taken together, our results reveal a critical role for melanin interaction with airway epithelium in shaping the host response to fungal and bacterial pathogens.