Lattice-sum methods are nowadays routinely used to calculate electrostatic interactions in explicit-solvent simulations of biomolecular systems. These methods account for the long-range component of Coulomb interactions by assuming that they are exactly periodic within the simulated system. When lattice-sum methods are applied to inherently nonperiodic systems such as solutions, it is legitimate to question the validity of this assumption. The present study investigates the nature and magnitude of periodicity-induced artifacts in a set of 12 independent explicit-solvent molecular dynamics simulations of a small protein and an oligonucleotide, at different temperatures and ionic concentrations. Configurations sampled during these simulations are analyzed using continuum electrostatics to evaluate the corresponding periodicity-induced perturbation of the electrostatic free energy. The results suggest that, for the systems considered, artificial periodicity induces a nonnegligible free-energy bias in the sampled ensembles, but that this energetical bias results in no major structural perturbation. The perturbation is also found to be smallest when a minimal (neutralizing) set of counterions is included during the simulation.