Pyridine, its N-oxide, and their derivatives are exciting classes of organic bases. These compounds show widespread biological activity, and they are often used in synthesis. In this work results on theoretical calculations of acid dissociation constants as pK(a) of pyridine, its N-oxide, and their derivatives were done based on the thermodynamic cycle in water and acetonitrile. Additionally, gas-phase basicity (GB) and proton affinity (PA) values were computed for systems studied. All pK(a) values were obtained using B3LYP, M06-2X, and G4MP2 methods in the gas phase, which were combined with the PCM model calculations (at the Hartree-Fock method) and with the use of four different scale factors alpha. Theoretical GB, PA, and pKa values were then compared with the available experimental ones. Results obtained from B3LYP and M06-2X methods are quite similar and compatible with experimental ones in terms of quality with correlation coefficients values R-2 higher than 0.9, whereas results received from G4MP2 deviate strongly. The calculated pK(a) MSD) between both theoretically and experimentally available pK(a) values of systems studied were also computed. The RIVISD values are lower than 0.8 for the best results, suggesting that the theoretical model presented in this work is promising for applications for pK(a) calculations of different classes of compounds.