Hibiscus sabdariffa is used as potent phytochemical agent due to its phenolic composition. On the other hand, Supercritical Fluid Extraction (SFE) is considered a green extraction technique that provides a selective extraction using a supercritical solvent. In this work, extraction parameters such as temperature, pressure of CO2 and percentage of co-solvent were evaluated on the chemical composition of Hibiscus sabdariffa by Response Surface Methodology (RSM). After that, individual compound concentration was determined by HPLC-ESI-TOFMS. This design, allowed found the optimal conditions for total phenolic and organic acids content. Each chemical group showed different behavior against SFE. Despite organic acids exhibited an irregular trend; the quadratic model was fitted for total phenolic compounds. Therefore, SFE has demonstrated to be a suitable and selective technique to maximize the extraction of several phytochemical compounds from H. sabdariffa calyces.