Supercritical carbon dioxide (SC−CO2) has been used as solvent in the ethanolysis of fish oil rich with omega-3 polyunsaturated fatty acids (n-3 PUFAs) by Lipozyme 435. The effect of experimental conditions: initial ethanol-to-oil molar ratio (MR, 6:1-76:1), pressure (10–30 MPa), and temperature (323–343 K) on the reaction performance has been studied. Experimental results have been fitted to a kinetic model based on a Ping Pong Bi Bi mechanism. High accumulation of monoacylglycerides (MAGs) has been observed in short reaction times (90 min at MR = 76:1, 10 MPa, 323 K). Subsequent purification of reaction products by supercritical fluid extraction (SFE) in the experimental range 10–28 MPa and 298–333 K yielded an extract rich with fatty acid ethyl esters (FAEE) (up to 99.46%wt.), and a raffinate with up to 82.25%wt. MAG and 49.5%wt. n-3 PUFAs.