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Moderate to vigorous physical activity (MVPA) interventions reduce the severity of obstructive sleep apnoea (OSA); however, little epidemiological research exists to confirm these findings. 789 participants from the population-based Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study underwent polysomnography. MVPA was assessed using the Active Australia questionnaire, which was completed when participants were first recruited to the MAILES study (2002–2006), and again in 2010. Multinomial logistic regressions established odds ratio between OSA severity categories with MVPA, whilst adjusted linear models determined associations between OSA metrics with MVPA. Cross-sectionally, each hour of MVPA was associated with reduced severity of mean oxygen desaturation (unstandardised β (B)=−0.002, p=0.043) and reduced time below 90% oxygen saturation (B=−0.03, p=0.034). Longitudinally, each hour increase in MVPA was associated with a 4% reduction in the odds of severe OSA and less severe mean oxygen desaturation (B=−0.003, p=0.014), time below 90% oxygen saturation (B=−0.02, p=0.02), and mean duration of apnoeas (B=−0.004, p=0.016). MVPA is associated with reduced hypoxaemia in a cohort of community dwelling males, approximately half of whom had untreated OSA. As nocturnal intermittent hypoxaemia is associated with cardiometabolic disorders, MVPA may offer protection for patients with OSA.