High hydrostatic pressure processing (HHP) is extensively applied for the non-thermal pasteurization of foods. One notable feature of HHP mediated inactivation of microbes is the large variation in lethality between strains and the influence of the food matrix. In the following it was hypothesized that the barotolerance of Shiga Toxin producing Escherichia coli could be correlated to tolerance to low water activity environments. The study evaluated the barotolerance of members of the Top 6 STEC serotypes and found variation with O26: H11 and O45: H2 exhibiting higher tolerance to pressure compared to the other bacterial types tested. A negative correlation was found between resistance to high pressure and the NaCl concentration under which E. coli could grow under. For example, E. coli O26: H11 exhibited the highest tolerance to pressure, within 300 MPa, but could only grow under NaCl up to 2.4% w/v. In contrast, E. coli O121: H19 was sensitive to pressure, but could grow in the presence of 6% NaCl. The results suggested that the induction of the stress-response was the likely reason for high barotolerance in salt sensitive strains vs resistant. It was also found that supplementing the suspension medium with amino acids, sugar alcohols and starch could increase the barotolerance of E. coli. Although it is possible that the solutes acted directly as osmolytes it is also proposed that metabolic products and other indirect protective mechanisms were also operating. The study suggests that early induction of the osmotic stress response can be used to predict the resistance to high hydrostatic pressure.