Stress increases inflammation but whether adherence to Mediterranean diet counteracts this association and how early can these effects be observed is not well known. We tested whether (1) cortisol is associated to inflammation, (2) cortisol is associated to the adolescent Mediterranean diet score (aMDS), (3) aMDS lessens inflammation, (4) aMDS associates with cortisol levels and inflammation. Two hundred and forty-two adolescents (137 females; 12.5–17.5 years old) provided salivary cortisol,

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... od and 2-day 24-h dietary recall from which aMDS was derived. Cortisol levels were associated with increased tumor necrosis factor (TNF-α B = 11.887, p = 0.001) when adjusted for age, gender, parental education and body mass index (BMI). Moreover, cortisol levels were inversely associated to adherence to the Mediterranean Diet (B = −1.023, p = 0.002). Adolescents with higher adherence to aMDS had lower levels of interleukins (IL) IL-1, IL-2, IL-6 and TNF-α, compared to those who did not adhere. The association between cortisol and TNF-α was no longer significant when aMDS was included in the model (B = 6.118, p = 0.139). In addition, comparing lower and higher aMDS groups, the association between cortisol and TNF-α was only observed in those with lower aMDS adherence. Our study suggests that adherence to the Mediterranean Diet may counteract the effect of stress on inflammatory biomarkers which may contribute to decreasing the risk of future mental health.