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BACKGROUND/OBJECTIVES: Antioxidants and polyunsaturated fatty acids (PUFAs) have a role in the human immune defense and may affect the susceptibility to upper respiratory tract infection (URTI). To examine dietary intake of vitamin C, vitamin E, selenium, zinc and PUFAs in relation to URTI incidence in a prospective cohort study. SUBJECTS/METHODS: A total of 1533 Swedish women and men aged 25-64 years were followed for nine months during 2011-2012. Information on dietary intake was assessed through a web-based food frequency questionnaire, and events of URTI were self-reported prospectively as they occurred. Cox proportional hazards regression was applied to obtain incidence rate ratios with 95% confidence intervals. RESULTS: The mean number of URTI events was 0.9 among all participants, 1.0 among women and 0.7 among men. In women, the incidence rate ratios ( 95% confidence interval) for high compared with low intake were 0.69 (0.55-0.88) for vitamin C, 0.77 (0.62-0.96) for vitamin E, 0.57 (0.39-0.83) for docosahexaenoic acid (DHA) and 0.80 (0.65-0.99) for arachidonic acid ( AA). No association was found for selenium or zinc among women. In men, an increased URTI incidence was seen with medium vitamin E intake (1.42 (1.09-1.85)) and high zinc intake (1.50 (1.04-2.16)). No association was found for vitamin C, selenium or PUFAs among men. CONCLUSIONS: We found an inverse association of URTI incidence among women for vitamin C, vitamin E, DHA and AA intake and a positive association among men for vitamin E and zinc intake. The observed gender differences warrant further investigation.