β-Glucans are abundant bacterial, yeast, and fungal cell wall polysaccharides that have been shown to activate the immune system. Establishment of an occupational exposure limit (OEL) for β-glucan exposure is critical to the protection of worker health, as these exposures have been linked to immunosuppressive and inflammatory reactions and possibly the development of respiratory diseases. Detectable concentrations of β-glucans have been identified in common occupational inhalation exposure scenarios, such as in the agricultural and waste management sectors. However, no published exposure benchmarks for inhalation of β-glucans are available for workers or the general population. Thus, a health-based OEL for inhalation exposure of workers to β-glucans was derived based on consideration of human and non-human effect data for this class of compounds and contemporary risk assessment methods. The weight of the evidence indicated that the available data in humans showed significant methodological limitations, such as lack of a representative study size, appropriate control population, and clear dose-response relationship. Thus, an OEL of 150 ng/m³ was derived for β-glucans based on the most relevant nonclinical study. This OEL provides an input to the occupational risk assessment process, allows for comparisons to worker exposure, and can guide risk management and exposure control decisions.