In this study, a central composite design (CCD) allowed the optimal operating conditions to be determined for a new continuous process of spa water disinfection based on an innovative silver composite material. This systemic approach investigated the combined influences of water flow rate, material, and salt concentrations on bactericidal performance at spa water temperature (37°C) using Escherichia coli and Staphylococcus epidermidis as surrogates. The silver desorption was also simultaneously characterized. This multiparametric study highlighted the major contribution of supported silver to the antibacterial action, compared with that of desorbed silver, and enabled a predictive model to be developed that proposed the best and worst process operating conditions regarding bactericidal performances. These conditions were experimentally validated. Antibacterial action was favored by high water flow rate, high material concentration, and low salt concentration. These conditions were shown to improve the contact frequency between microorganisms and active silver material surface. In such conditions, no significant influence from the presence of organic matter or lowered temperature was observed on the disinfection performance.