In this study we show that the spectral distortion of OA signals, caused by wavelength-dependent optical attenuation inside the bulk tissue, can be corrected based on OA imaging, when using multiple-irradiation sensing. The tissue is modeled as a strongly scattering background, in which a discrete number of blood vessels, characterized by a higher absorption than the background, are sparsely distributed. OA signals generated by these vessels, which serve as intrinsic “fluence detectors”, are recorded as a function of irradiation position. In order to account for realistic situations, we have developed a semi-empirical light diffusion model that is fitted to the recorded signals, so as to determine the background’s optical effective attenuation coefficient for arbitrarily shaped tissues. The experimental validation of this model was performed on tissue-mimicking phantoms. The results demonstrate a successful correction of the measured OA spectrum of the embedded vessel-like inclusions, in the presence of lateral geometrical boundaries and when vessel-like absorbing structures influence the light propagation.