Cyclooxygenase 2 (COX-2) and the production of cytokines/chemokines are important targets for the modulation of the inflammatory response. Although a large variety of inhibitors of these pathways have been commercialized, some of those inhibitors present severe side effects, governing the search for new molecules, as alternative anti-inflammatory agents. This study was undertaken to study an hitherto not evaluated group of flavonoids, concerning its capacity to inhibit COX-1 and COX-2 enzymes, as well as to inhibit the production of the cytokines and a chemokine, in a complex matrix involved in the systemic inflammatory process, the blood, aiming the establishment of a structure-activity relationship. The results obtained reveal promising flavonoids for the modulation of the inflammatory process, namely the ones presenting a catechol group in B ring, as some flavonoids were able to simultaneously inhibit the production of inflammatory prostaglandin E2 and pro-inflammatory cytokines.