In order to understand the ion transport in a continuous cross-flow shock electrodialysis process better, numerous theoretical studies have been carried out. One major assumption involved in these models has been that of a constant surface charge. In this work, we considered the influence of charge regulation, caused by changes in salt concentration, on the performance of a shock electrodialysis cell. Our results show that, by including charge regulation, much higher potentials need to be applied to reach the same degree of desalination, compared to the constant surface charge model. Furthermore, we found that operating at higher potentials could lead to substantial Joule heating and therefore temperature increases. Although somewhat lower potentials were required in the nonisothermal case versus the isothermal case with charge regulation, the required energy input for desalination is still much higher than the thermodynamic minimum. This works highlights the important role charge regulation can play in a shock electrodialysis process.