BACKGROUND/OBJECTIVES: We have previously described that low adherence to the Mediterranean diet (MD) in elderly patients admitted in internal medicine wards is linked to poorer clinical outcomes. This investigation was designed to explore whether adherence to the MD is related to circulating markers of redox balance and inflammation in this clinical scenario. METHODS: A cross-sectional study was performed on 306 acute old patients hospitalized in internal medicine wards. Adherence to the MD was estimated by the Italian Mediterranean Index (IMI). The circulating markers of redox balance were assessed in serum and erythrocytes and correlated with inflammatory markers across different MD adherence groups. RESULTS: Compared to the patients with high adherence, those with low adherence to the MD exhibited severely impaired redox balance, as evidenced by a higher GSSG/GSH ratio and increased serum hydroxynonenal/malondialdehyde-protein adducts. No modifications were described in the expression of antioxidant enzymes in peripheral blood mononuclear cells. Patients with low adherence to the MD exhibited a higher neutrophil-to-lymphocyte ratio and markers of systemic inflammation, as well as raised levels of interleukin-6 and tumor necrosis factor, compared to those with high MD adherence. A strong association was observed between the circulating markers of redox balance and inflammation/immune response, with the highest regression coefficients found in the low adherence group. CONCLUSIONS: Old patients admitted to internal medicine wards with low adherence to the MD display unfavorable profiles of the circulating markers of redox balance and inflammation. It is conceivable that such effects on redox balance can be linked to the high polyphenol content of MD. This study supports the rationale for intervention trials that attest to the effectiveness of MD as a nutritional strategy for disease prevention.