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In this double-blind, randomized, placebo-controlled parallel study, we examined the effect of dairy-based beverages (250 mL/day) containing 250 mg of dispersible baker's yeast β-glucan (Wellmune) compared to a macronutrient- and calorie-matched control on upper respiratory tract infection (URTI) in marathon runners. Healthy adults running in the 2017 Austin Marathon consumed either β-glucan ( N  = 132) or control ( N  = 225) for the 45 days prior to, day of, and 45 days after the marathon (91 days total). Participants completed a daily online survey assessing compliance, training status, and URTI symptoms. URTI occurrence and severity were evaluated using the Jackson Index and confirmed by the study physician. No significant differences in average duration and number of URTI episodes were found between β-glucan and control. However, those who completed the study per protocol on the β-glucan beverage reported significantly fewer URTI symptomatic days (3.43 ± 6.44 days, max 27 days) compared to those on control beverage (3.84 ± 6.84 days, max 49 days). Total URTI severity was significantly lower for β-glucan (4.52 ± 1.61) compared to control (5.60 ± 2.23). Specifically, lower ( p  < .05) severity ratings for nasal discharge and sore throat were reported for β-glucan compared to control. Average missed postmarathon workout days due to URTI were significantly less for β-glucan (0.09 ± 0.38 days, max 2 days) compared to control (0.36 ± 1.40 days, max 10 days). Overall, consumption of dairy-based beverages containing dispersible yeast β-glucan decreased URTI symptomatic days, severity of specific URTI symptoms, and missed postmarathon workout days due to URTI, without affecting duration and number of URTI episodes.