The inactivation of four different microorganisms, Escherichia coli, Bacillus mycoides, Staphylococcus aureus and Candida albicans, inoculated in simulated (SWW) and real winery wastewaters (RWW), was assessed by the first time using free sulphate and hydroxyl radicals from photolytic (UV-A LED radiation; 370 nm) and metal [Fe(II) or Co(II)] activation of peroxymonosulphate (PMS). The experimental conditions tested were [PMS] ¼ 0.1 mM and [Fe(II) or Co(II)] ¼ 0.1 mM and pH 5.0 for the inactivation of microorganisms in SWW. However, due to the complexity of the water matrix, not unexpectedly, a fivefold concentration of reagents was required to inactivate the same organisms in RWW. In addition, compared to the bacteria, the fungus C. albicans presented a higher oxidative stress resistance to the treatments, and different experimental conditions were necessary to inactivate these cells. After 90 min, the photolytic activation of PMS through UV-A LED radiation achieved complete inactivation of E. coli, followed by S. aureus (z4 log) and B. mycoides (z3 log). Total inactivation of C. albicans was also achieved, but with higher dosages of PMS (10 mM). The metal activation of PMS through the use of a transition metal [Fe(II) or Co(II)] accelerated the inactivation rate, particularly in the first minutes of exposure time. These treatments reached between 1 and 3 log inactivation of microorganisms in the first minute of the experiment. In addition, the use of Co(II) as promoter in the activation of PMS, was more effective in the inactivation of S. aureus and C. albicans than activation with Fe(II). Since linear mathematical models do not adjust satisfactorily to inactivation results in all cases, different mathematical models were tested to fit the experimental inactivation data. In general, the Hom model correctly fits the inactivation results of the four microorganisms in all applied treatments. However, other models such as Biphasic and Double Weibull fit acceptably as well.