Abstract The decontamination and sanitation methods currently used are mainly antimicrobial ineffective, generate high costs with a high consumption of water and chemicals (additives). As an alternative, non-thermal plasma at atmospheric pressure could be a versatile tool. Therefore, a pilot-scaled set-up based on a microwave-plasma source that generates plasma processed air (PPA), a gaseous mixture which contains manifold RNS-based chemical compounds gaining, among others, the antimicrobial effectivity of that mixture. The PPA was introduced to a water-processing device (WPD) to enrich tap water. By this way, plasma processed tap water (PPtW), which can be applied for the decontamination of packaging material, fresh produce and processing equipment, was generated. This is a new and innovative method for the generation of antimicrobial active plasma processed water. In our experiments, the native contamination of fresh-cut lettuce treated with PPtW in a common washing process and the microbial load of the washing water itself was investigated. Different treatment scenarios showed the influence of PPtW to the fresh-cut lettuce and the washing water as well as the hygienic problems of recontamination during the washing process. The characteristics of plasma and its generated cocktail of long living chemical compounds in air and in water leading to a significant bacterial inactivation and offering a wide range of possible applications. Industrial relevance The safety, quality and shelf life of freshly cut vegetables greatly depend on the microbial load, especially with phyto and human pathogens, of the produce as well as the hygienic design of production device and good handling and production practice. This study shows that the application of PPW/PPtW, as a promising non-thermal sanitation technology, enables the inactivation of native contamination on fresh-cut lettuce in industrial relevant level. It further describes the impact of the necessity of hygienic environment during production to avoid cross- and re-contamination. The results contribute to the understanding and product-specificity of PPW-induced effects on safety, quality and shelf life of fresh cut lettuce and could be a basis for a possible industrial implementation and complement of common technologies.