The use of high pressure on fruits and vegetables is today widely studied as an alternative to the traditional thermal preservation techniques, with the aim of better preserving nutritional and organoleptic properties. The use of high hydrostatic pressures (400–600 MPa; 1–5 min; room temperature) was tested on the physicochemical and structural properties of blueberries, in comparison to raw and blanched samples. High hydrostatic pressures led to higher tissue damages than blanching, related to the intensity of the treatment. The cellular damages resulted in leakage of intracellular components, such as bioactive molecules and enzymes. As a consequence, among the high pressure treatments, the resulting antioxidant activity was higher for samples treated for longer times (5 min). Pectinmethyl esterase (PME), deactivated by blanching, but strongly barotolerant, was more active in blueberries treated with the more intense high pressure conditions. Blueberry texture was better retained after high pressure than blanching, probably because of the PME effect. Blueberry color shifted towards purple tones after all of the treatments, which was more affected by blanching. Principal component analysis revealed the mild impact of high pressure treatments on the organoleptic properties of blueberries.