The Coulomb interactions in molecular simulations are inherently approximated due to the finite size of the molecular box sizes amenable to current-day compute power. Several methods exist for treating long-range electrostatic interactions, yet these approaches are subject to various finite-size-related artifacts. Lattice-sum methods are frequently used to approximate long-range interactions; however, these approaches also suffer from artifacts which become particularly pronounced for free-energy calculations that involve charge changes. The artifacts, however, also affect the sampling when plain simulations are performed, leading to a biased ensemble. Here, we investigate two previously described model systems to determine if artifacts continue to play a role when overall neutral boxes are considered, in the context of both free-energy calculations and sampling. We find that ensuring that no net-charge changes take place, while maintaining a neutral simulation box, may be sufficient provided that the simulation boxes are large enough. Addition of salt to the solution (when appropriate) can further alleviate the remaining artifacts in the sampling or the calculated free-energy differences. We provide practical guidelines to avoid finite-size artifacts.