A time-dependent density functional theory (TDDFT) and the second-order approximated coupled-cluster model with the resolution of identity approximation (RICC2) studies are reported here for some classes of squaraine derivatives. These compounds have a sharp electronic band, ranging from the visible to near-red part of the spectrum, with an high molar absorption coefficient. These features make them potential photosensitizers in the photodynamic therapy of cancer (PDT), in which a light source, a photosensitizer, and molecular oxygen ((3)O2) are combined to give cytotoxic singlet oxygen ((1)O2) as a final result in a photochemical process. For the examined structures, the introduction of different substituents (electron donating, electron withdrawing, or fused rings) in the parent molecule, in order to give different squaraine derivatives, changes the maximum absorption wavelength (λmax) from 620 to 730 nm, giving a near-red absorbing photosensitizer that can better penetrate human tissue to damage tumor cells. Theoretical results, obtained from both TDDFT/PBE0 and RICC2, are able to reproduce qualitatively the substitution effect on λmax, resulting in a useful tool for testing different structure modifications and, in general, for the molecular design of PDT photosensitizers. Calculated vertical excitation energies (singlet-singlet transitions) generally agree with experimental data within 0.3 eV. The singlet oxygen generation ability of these compounds requires that their triplet energy, for a type II reaction mechanism, should be greater than 0.98 eV. Theoretical triplet energies from the RICC2 method suggests that this requisite is fulfilled for all compounds, though the results are generally overestimated with respect to experiment by 0.7 eV, whereas TDDFT/PBE0 triplet energies, which are underestimated within 0.2 eV in few cases, lie close to the above-mentioned limit and can be considered suitable for PDT applications.