Coffee consumption is associated with reduced risk of conditions that share low-grade inflammation as their physiopathological basis. We therefore summarized the effects of coffee or coffee components on serum levels of inflammatory markers. Clinical trials assessing the effect of coffee, caffeine or other coffee components on inflammatory markers were searched without restriction to publication date. Fifteen studies (8 involving coffee and 7 caffeine) were included. Increased adiponectin levels were found in four of seven trials comparing filtered coffee/caffeinated coffee with placebo or comparing its levels at baseline and after consumption of medium or dark roasted coffee, but no change was seen in caffeine trials. None of the five studies assessing the effects of coffee found changes in C-reactive protein (CPR), but one out of three trials found decreased CPR levels in response to caffeine. Interleukin (IL)-6 was increased by caffeinated coffee compared with placebo in one of four coffee trials, and by caffeine in three out of five studies. Caffeine increased IL-10 levels in two of three trials. These data suggest a predominant anti-inflammatory action of coffee but not of caffeine consumption. Moreover, the proinflammatory and anti-inflammatory responses to caffeine point to its complex effects on the inflammatory response.