Subclinical inflammation is frequently noted in chronic diseases such as diabetes, cardiovascular disease (CVD) and obesity. Accumulating epidemiological evidence demonstrates that diets rich in vegetables and fruits, e.g., cherries, may significantly reduce the risk of chronic disease, in part, via antioxidant and anti-inflammatory activities. In this randomized, placebo-controlled crossover study, we recruited 10 at-risk participants (38.1 ± 12.5 years; 8 females, 2 males) with BMI >25.0 kg m-2 (32.2 ± 4.6 kg m-2; 5 obese, 5 overweight) to consume 240 mL (8 ounces) daily of either 100% tart cherry juice (TCJ) or an alternate placebo beverage, for 4 weeks with a 2-week intervening washout period before switching to the alternate beverage for four weeks. Fasting blood samples were collected at the beginning and end of each arm for measurement of biomarkers of inflammation. The erythrocyte sedimentation rate (ESR), an indicator of chronic inflammation, was significantly (p < 0.05) lower with TCJ than with the placebo beverage, which increased ESR by 19%. Mean baseline hsCRP, an indicator of acute inflammation, was 7.0 ± 5.2 mg L-1 and consumption of TCJ did not affect hsCRP levels. The chemokine MCP-1 and cytokine TNF-alpha were lower in participants after consuming TCJ compared to those consuming the placebo beverage. Plasma IL-6 and IL-l0 were not different between treatments. Collectively, the data suggest that authentic 100% TCJ may reduce biomarkers of inflammation often noted in chronic disease and may be a preferable dietary selection compared to artificially flavored beverages with added sugars.