Microalgae represent diverse branch of microorganism that can produce a wide range of unique functional ingredients that can be used in food, cosmetics, pharmaceuticals, and energy. Among them, Haematococcus pluvialis is known for accumulating the highest levels of a potent natural antioxidant, astaxanthin, which has demonstrated positive health effects. Therefore, the aim of numerous studies has been to develop novel and efficient extraction techniques to produce high-quality (purity and antioxidant activity) extracts, while complying with the Green Chemistry Principles. Supercritical CO 2 (scCO 2 ) emerges as an alternative to organic solvents because of its high selectivity and bioactivity-preserving qualities. Nevertheless, astaxanthin is a large molecule with low solubility in scCO 2 that usually requires long extractions at high pressures. Ethanol has been used as co-solvent to increase astaxanthin solubility in scCO 2 . In this work, a Box–Behnken experimental design was used to study the effects of operating pressure (20–35MPa), temperature (40–70°C), and ethanol content in scCO 2 (0–13%, w/w) on the yield, astaxanthin content, and antioxidant activity of H. pluvialis extract. Results showed that ethanol content in CO 2 has a more significant effect on all responses than pressure and temperature. These results lead us to investigate the effect of a further increase in ethanol content, up to the region of gas-expanded liquids. We studied the effects of temperature (30–60°C) and ethanol content (50–70%, w/w) at a fixed pressure (7MPa) on the same response variables using CO 2 -expanded ethanol (CXE). Results showed that temperature and ethanol content had a significant influence on astaxanthin yield and antioxidant activity. Also, the overall responses of CXE surpassed scCO 2 extractions to match conventional extraction with acetone, maintaining high quality extracts, thus validating the use of this new type of green technology for extraction of high-value compounds.