This study assessed the resistance to Ultraviolet light (UV) and Cold Atmospheric Plasma (CAP) of ten verocytotoxigenic Escherichia coli (VTEC) isolates and two laboratory non-pathogenic E. coli strains and monitored the effects that UV and CAP have on VTEC molecular composition by using Fourier transform infrared (FTIR) spectroscopy. In addition, serotype-related resistance patterns to different stresses (acid, alkaline, heat, high hydrostatic pressure, UV, CAP and biofilm formation ability) were determined through multivariate analysis of stress resistance parameters. While UV treatments were very effective in inactivating VTEC, with >5log reductions at the lowest intensity tested (15mJ) and low intraspecies variability, the efficacy of CAP treatments was more limited, with in general <3log reductions after a treatment of up to 3min in the lab-scale CAP equipment and larger interstrain variability. Two VTEC strains with non-sense mutations in the global stress response regulator rpoS showed an increased sensitivity to CAP at short treatment times, what suggests that RpoS is important for the cellular defensive response to this technology of preservation. Stepwise Discriminant Analysis (SDA) of FTIR spectra allowed the differentiation of untreated and treated samples based on a subrange of the spectral region w4 (1200 to 900cm−1), which suggests that the damage inflicted to the cells is focused, both for UV and CAP treatments, in nucleic acids and the cell wall. Principal Component Analysis (PCA) of stress resistance parameters allowed the identification of significant associations between VTEC serotypes and their stress resistance patterns. Strains of the serotype O157, more commonly associated with human disease, were in general more resistant to food-related stresses than strains of other serotypes when they had a functional RpoS, emphasizing the influence that stressors may have in the epidemiology, ecology and disease-causing potential of VTEC.