The extraction of lipophilic molecules from sugarcane straw is an essential component as a part of a holistic biorefinery. Bearing this in mind, this work focuses on supercritical CO2 (ScCO2) extraction assisted by ultrasound as a clean efficient process. The effects of operating parameters temperature (40 - 60 °C) and ultrasound power (400 W – 800 W) on the ScCO2 global yield and Field emission scanning electron microscopy (FESEM) on solid residue remaining were studied. The maximum global yield of the extracts (0.90 ± 0.10 g extract/ g straw) was obtained at 60 ºC, and 800 W. FESEM was used to analyze the solid residue remaining with and without ultrasound and showed that ultrasound disturbs the cell walls, enhancing the release of the extractable compounds. Statistical analysis showed that the temperature was the parameter that influenced the global yield of the extracts. This technology crucially improves the downstream conversion since ScCO2 not only can be used as an extraction solvent, but also for the pre-treatment. Sugarcane straw lipophilic molecules can be useful in a host of applications, ranging from cosmetics to hard wax polishes, lubricants, coatings, and plasticizers.