The difference in electrostatics and reduction potentials between manganese ortho-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP) and manganese meta-tetrakis(N-ethylpyridinium-3-yl)porphyrin (MnTE-3-PyP) is a challenging topic, particularly because of the high likelihood for their clinical development. Hence, a detailed study of the protolytic and electrochemical speciation of Mn^II–IVTE-2-PyP and Mn^II–IVTE-3-PyP in a broad pH range has been performed using the combined spectrophotometric and potentiometric methods. The results reveal that in aqueous solutions within the pH range ∼2–13 the following species exist: (H₂O)Mn^IITE-m-PyP⁴⁺, (HO)Mn^IITE-m-PyP³⁺, (H₂O)₂Mn^IIITE-m-PyP⁵⁺, (HO)(H₂O)Mn^IIITE-m-PyP⁴⁺, (O)(H₂O)Mn^IIITE-m-PyP³⁺, (O)(H₂O)Mn^IVTE-m-PyP⁴⁺ and (O)(HO)Mn^IVTE-m-PyP³⁺ (m = 2, 3). All the protolytic equilibrium constants that include the accessible species as well as the thermodynamic parameters for each particular protolytic equilibrium have been determined. The corresponding formal reduction potentials related to the reduction of the above species and the thermodynamic parameters describing the accessible reduction couples were calculated as well.