A low density supercritical anti-solvent (SAS) precipitation of zeaxanthin palmitates (ZP) from Lycium barbarum (LB) to increase the purity of zeaxanthin palmitates in precipitates and to reduce the mean particle size of those precipitates was studied. The experimental data herein reveal that the purity of zeaxanthin palmitates increased with pressure, and total yield and purity increased with feed flow rate, but the effect of the anti-solvent time was trivial. A three-factor center composited schemed response surface method was used to study the effects of pressure, feed flow rate and time on total yield, purity, recovery and particle size of the precipitates. A precipitated powder with a mean particle size of approximately 2800 nm, a purity of 92.5%, a total yield of 66% and a recovery of 71%, was obtained at a pressure of 150 bar, a feed flow rate of 0.2 mL/min and an anti-solvent injection time of 48 min. This study demonstrated that low-density SAS precipitation promotes the purity of micro-sized ZP precipitates.