Effect of high pressure (HP) treatment on the antimicrobial properties and the structure of nisin was evaluated. Nisin solutions at pH 2.8 or 6.1 were treated by HP at 500 MPa – 10 min – 20 °C and their antimicrobial potency was determined. It appeared that HP clearly impacted the antimicrobial activity of nisin, with respective activity loss of 22.5% and 49.9% at pH 2.8 and 6.1. Structural analysis of nisin by circular dichroism and Fourier transform-infrared spectroscopies revealed that the decrease of nisin antimicrobial activity was likely due to the unfolding of the protein induced by HP. A loss of nisin β-turns structure, particularly significant at neutral pH, was linked to the drastic drop in antimicrobial activity, as these structures are implicated in the nisin interaction with the bacterial membrane.Industrial relevanceThe combination of nisin and high pressure (HP) can be use at an industrial scale to inactivate bacteria. Nisin is allowed as a food additive (E234) and can be added at a final concentration ranging from 120 to 500 IU/g, depending on the product. In this work, we showed that HP can induce a significant reduction of nisin activity (-22.5% at pH 2.8 and -49.9% at pH 6.1). Therefore, this activity loss could be taken into account to manage the final nisin concentration in HP-treated food products.