This study assessed the magnitude of variations in the concentrations of disinfection by-products, specifically trihalomethanes and haloacetic acids, which occur in two UK water distribution networks of different sizes due to changes in the hydraulic operation of the networks. These operational changes included varying the fill levels of water storage tanks and pumping conditions within the network. This was investigated through modelling which combined a conventional distribution network flow model (EPANET) with previously developed models for disinfection by-product formation, and using network information obtained from water company partners. The modelling demonstrated that there is the potential for significant variations in disinfection by-product concentrations, up to a 40% change in some simulations, due to what may be considered routine variability in the hydraulic operation of the network. Smaller networks may be especially susceptible to these variations. These findings may influence how water companies plan disinfection by-product monitoring programmes for regulatory reporting.