The high pressure tolerance of cysts of Artemia salina was investigated up to several GPa in water. No survival was observed after exposure to 1.0 GPa for 15 min. After exposure to 2.0 GPa for the same time duration, the hatching rate had recovered to 33%, but decreased to 8% following compression at 7.5 GPa. This contrasts with results using Fluorinert™ as the pressure-transmitting medium where 80–88% recovery was observed. The lower survival rate in water is accompanied by swelling of the eggs, indicating that liquid H2O close to the ice-VI crystallization pressure penetrated inside the eggs. This pressure exceeds the stability limit for proteins and other key biomolecules components within the embryos that could not be resuscitated. Rehydration takes several minutes and so was not completed for all samples compressed to higher pressures, prior to ice-VI formation, resulting in renewed survival. However H2O penetration inside the shell resulted in increased mortality.