This study evaluated the effects of 10-day broccoli (250 g/day) intake on dietary markers and markers of inflammations in young male smokers. A dietary intervention study with a repeated measures crossover design was conducted. Circulating levels of carotenoids, folate, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 6 receptor (IL-6sR) and adiponectin were measured. Broccoli intake significantly increased plasma levels of folate (+17%) and lutein (+39%), while no significant effect was observed for TNF-α, IL-6, IL-6sR or adiponectin. Plasma CRP decreased by 48% (post-hoc analysis, p < 0.05) following broccoli diet; this resulted to be independent from the plasma variations in lutein and folate. An inverse correlation between lycopene, TNF-α and IL-6sR was observed at baseline. In conclusion, broccoli consumption may reduce CRP levels in smokers, consistent with epidemiologic observations that fruit and vegetable intake is associated with lower circulating CRP concentrations.