The health benefits of orange juice (OJ) consumption are attributed in part to the circulating flavanone phase II metabolites and their microbial-derived ring fission phenolic catabolites. The present study investigated these compounds in the bloodstream after acute intake of 500 mL of OJ. Plasma samples obtained at 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h after OJ intake were analysed by HPLC-HR-MS. Eleven flavanone metabolites and 36 phenolic catabolites were identified and quantified in plasma. The main metabolites were hesperetin-3'-sulfate with a peak plasma concentration (C-max) of 80 nmol/L, followed by hesperetin-7-glucuronide (C-max 24 nmol/L), hesperetin-3'-glucuronide (C-max 18 nmol/L) and naringenin-7-glucuronide (C-max 21 nmol/L). Among the main phenolic catabolites to increase in plasma after OJ consumption were 3'-methoxycinnamic acid-4'-sulfate (C-max 19 nmol/L), 3-hydroxy-3-(3'-hydroxy-4'-methoxyphenyl)propanoic acid (C-max 20 nmol/L), 3-(3'-hydroxy-4'-methoxyphenyl)propanoic acid (C-max 19 nmol/L), 3-(4'- hydroxyphenyl)propanoic acid (C-max 25 nmol/L), and 3(phenyl)propanoic acid (C-max 19 nmol/L), as well as substantial amounts of phenylacetic and hippuric acids. The comprehensive plasma pharmacokinetic profiles that were obtained are of value to the design of future ex vivo cell studies, aimed at elucidating the mechanisms underlying the potential health benefits of OJ consumption.