Investigation of the effect of high-pressure processing (HPP) at very short time on the inactivation of Listeria innocua was conducted as well as the effect on texture and microstructure. Lipid oxidation, color and background bacterial flora were studied as well. HPP at 700–900 MPa for 10 s increased the inactivation of L. innocua in cold smoked salmon from 4500 cfu / g to nondetectable level (<0.3 cfu / g). L. innocua was more sensitive to HPP than the background flora tested. The product presented good microbiological quality and there was no indication of lipid oxidation. The effect of HPP on the redness of the product was not observed, however immediate effect on the lightness was noticed and the salmon becomes lighter in color as a function of both time and pressure. The effects on the microstructure increased with both time and pressure and were most significant at 900 MPa and 60 s. The effect on microstructure coincides with the reduction of the bacteria. The knowledge from this study provides information for the industry on the development of HPP at 400–900 MPa with short pressure time of less than 60 s.