Dietary fiber may modulate the environment of the intestinal lumen, alter the intestinal microflora populations, and influence the immune response and disease risk. Epidemiological investigations have suggested that higher fiber intake is associated with lower overall mortality, in particular from cardiovascular and digestive tract diseases. Here a panel of 17 cytokines and chemokines were measured in plasma of 88 cancer-free subjects sampled within the Italian EPIC-Italy cohort. A statistically significant inverse association (p-trend = 0.01) was observed for cereal fiber and cytokines included in the main factor in factor analysis (IL-1β, IL-4, IL-5, IL-6, IL-13, and TNF-α), which alone explained 35.5% of variance. Our study suggests that fiber intake, especially cereal fiber, may be associated with a decreased level of pro-inflammatory cytokines.