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BACKGROUND: Poor sleep is associated with an increased risk of infections and all-cause mortality but the causal direction between poor sleep and respiratory infections has remained unclear. We examined if poor sleep contributes as a causal risk factor to respiratory infections.METHODS: We used data on insomnia, influenza and upper respiratory infections (URIs) from primary care and hospital records in the UK Biobank (N â‰ˆ 231,000) and FinnGen (N â‰ˆ 392,000). We computed logistic regression to assess association between poor sleep and infections, disease free survival hazard ratios, and performed Mendelian randomization analyses to assess causality.FINDINGS: Utilizing 23 years of registry data and follow-up, we discovered that insomnia diagnosis associated with increased risk for infections (FinnGen influenza Cox's proportional hazard (CPH) HR = 4.34 [3.90, 4.83], P = 4.16 Ã— 10, UK Biobank influenza CPH HR = 1.54 [1.37, 1.73], P = 2.49 Ã— 10). Mendelian randomization indicated that insomnia causally predisposed to influenza (inverse-variance weighted (IVW) OR = 1.65, P = 5.86 Ã— 10), URI (IVW OR = 1.94, P = 8.14 Ã— 10), COVID-19 infection (IVW OR = 1.08, P = 0.037) and risk of hospitalization from COVID-19 (IVW OR = 1.47, P = 4.96 Ã— 10).INTERPRETATION: Our findings indicate that chronic poor sleep is a causal risk factor for contracting respiratory infections, and in addition contributes to the severity of respiratory infections. These findings highlight the role of sleep in maintaining sufficient immune response against pathogens.FUNDING: Instrumentarium Science Foundation, Academy of Finland, Signe and Ane Gyllenberg Foundation, National Institutes of Health.