The solvent effect has been studied at the PBEO/CEP-121G level of theory on different intramolecular and intermolecular density functional global reactivity indexes for a set of substituted nickel plithalocyanines (NiPc(X)(n); X is the substituent). For all the indexes analyzed, we found that solvent plays a nonnegligible role: in some molecules it induces a stabilization, while in others it has a destabilizing effect. However, we also found along the whole set of NiPc(X), molecules that the presence of the solvent leads to the same overall trend obtained in the gas phase. To rationalize the behavior of the set NiPc(X)(n), we also did an analysis of the partial energy contributions to the total energy considering the environment variable given by the solvent and the chemical variable given by the substituent.