Chlorogenic acids (CGA) are abundant phenolic compounds in coffee, with caffeoylquinic (CQA), feruloylquinic (FQA), and dicaffeoylquinic (diCQA) acids being the major subclasses. Despite the potential biopharmacological properties attributed to these compounds, little is known about their bioavailability in humans. In this study, we evaluated the distribution profile of the major CGA isomers and metabolites in plasma and urine of 6 healthy adults for 4 h after brewed coffee consumption. Three CQA isomers and 3 diCQA isomers were identified in the plasma of all subjects after coffee consumption, whereas 2 FQA were identified in only 1 subject. Two plasma concentration peaks were observed, the first at 0.5–1.0 h and the second at 1.5–4.0 h after coffee consumption. The molar ratio CQA:diCQA was 12.2 in the brewed coffee, whereas in plasma it ranged from 0.6–2.9. The molar ratios 5-CQA:3-CQA and 5-CQA:4-CQA were consistently higher in plasma than in the brew. The main CGA metabolites identified in urine after coffee consumption were: dihydrocaffeic, gallic, isoferulic, ferulic, vanillic, caffeic, 5-CQA, sinapic, ρ-hydroxybenzoic, and ρ-coumaric acids (gallic and dihydrocaffeic acids being the major ones). This study indicates that the major CGA compounds present in coffee are differentially absorbed and/or metabolized in humans, with a large inter-individual variation. Moreover, urine does not appear to be a major excretion pathway of intact CGA compounds in humans.