BACKGROUND: We recently showed that calcitriol increases oxidative and inflammatory stress; moreover, inhibition of calcitriol with high-calcium diets decreased both adipose tissue and systemic oxidative and inflammatory stress in obese mice, whereas dairy exerted a greater effect. However, these findings may be confounded by concomitant changes in adiposity. OBJECTIVE: The objective of this study was to evaluate the acute effects of a dairy-rich diet on oxidative and inflammatory stress in overweight and obese subjects in the absence of adiposity changes. DESIGN: Twenty subjects (10 obese, 10 overweight) participated in a blinded, randomized, crossover study of dairy- compared with soy-supplemented eucaloric diets. Two 28-d dietary periods were separated by a 28-d washout period. Inflammatory and oxidative stress biomarkers were measured on days 0, 7, and 28 of each dietary period. RESULTS: The dairy-supplemented diet resulted in significant suppression of oxidative stress (plasma malondialdehyde, 22%; 8-isoprostane-F(2alpha), 12%; P < 0.0005) and lower inflammatory markers (tumor necrosis factor-alpha, 15%, P < 0.002; interleukin-6, 13%, P < 0.01; monocyte chemoattractant protein-1, 10%, P < 0.0006) and increased adiponectin (20%, P < 0.002), whereas the soy exerted no significant effect. These effects were evident by day 7 of treatment and increased in magnitude at the end of the 28-d treatment periods. There were no significant differences in response to treatment between overweight and obese subjects for any variable studied. CONCLUSION: An increase in dairy food intake produces significant and substantial suppression of the oxidative and inflammatory stress associated with overweight and obesity. This trial was registered at clinicaltrials.gov as NCT00686426.