Our previous study reported that different tea processing methods along with the age of coffee leaves affected antioxidant and anti-inflammatory bioactivities; however, identification of phytochemical components or associated mixtures that contribute to the anti-/pro-inflammatory activities was not determined. Herein, we report results of additional experiments designed to characterize the phytochemical composition of fractionated coffee leaf extract, derived from Japanese-style-green-tea-process-young (JGTP-Y) and black-tea-process-mature (BTP-M) leaves and related these data to anti-/pro-inflammatory activities. The aqueous fraction of BTP-M coffee leaves induced nitric oxide (NO), iNOS, COX-2, IL-6 and IL-10 production in Raw 264.7 cells. A 40% methanol fraction possessed greatest anti-inflammatory activities in IFN-γ and LPS treated Raw 264.7 cells (P < 0.05). The anti-inflammatory activities of coffee leaf fractions could not only be attributed to chlorogenic acids, mangiferin, rutin, and caffeine content, but possibly subtle interactions of mixtures of bioactive molecules.