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Background & Aims: A potential protection against COVID-19 by a high-quality dietary pattern is to be expected given the biological plausibility supporting the beneficial effects of an adequate dietary intake on the immune system. However, knowledge on the relationship between long-term maintained healthy dietary patterns, such as the Mediterranean diet, and the risk of SARS-CoV-2 infection is still sparse. We longitudinally assessed this association in a well-known Mediterranean cohort., Methods: We assessed 9,677 participants from the SUN Project, a prospective cohort of middle-aged university graduates in Spain. We inquired about a positive result in a COVID-19 diagnostic test during the months of February to December 2020. After excluding health professionals (HP), 5,194 participants were included in the statistical analyses (mean age: 52.6, SD: 12.4; 55.2% women). Food habits were assessed at baseline using a previously validated semiquantitative 136-item food frequency questionnaire. Adherence to the Mediterranean diet (cumulative average of 2 repeated measurements 10 years apart) was assessed using the 0-to-9 Mediterranean Diet Score (MDS). We used multivariable logistic regression models to estimate odds ratios and 95% confidence intervals for incident COVID-19 according to the MDS., Results: Among 5,194 non-HP participants, 122 reported to have received a positive COVID-19 diagnostic test. Participants with intermediate adherence to the Mediterranean diet (3 < MDS ≤ 6) had a significantly lower odds of developing COVID-19 (multivariable-adjusted OR = 0.50, 95% CI: 0.34-0.73), and those with the highest adherence (MDS > 6) exhibited the lowest risk (multivariable-adjusted OR = 0.36, 95% CI: 0.16-0.84, p for trend < 0.001) as compared with participants with MDS ≤ 3. This inverse association remained robust within subgroups and in sensitivity analyses. Notwithstanding, no significant associations were observed for health professionals (p for interaction = 0.06)., Conclusion: In conclusion, better adherence to the Mediterranean diet may be associated with a lower risk of COVID-19. Our results are applicable only to persons who are not health professionals., Competing Interests: Conflict of interest All authors declare no conflict of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)