We studied pulse energy density dependence of two distinctive clinical photosensitizers, Porfimer sodium and Talaporfin sodium, in terms of oxygen consumption, photodegradation in these photosensitizer solutions, and rat prostate cancer cell line photocytotoxicity. The transient transmittances during the pulsed irradiation to these photosensitizer solutions were measured with the pulse energy densities ranging from 0.31 to 31 mJ/cm2. We revealed that Talaporfin sodium was easier to produce absorption saturation than Porfimer sodium. The significant suppression of Talaporfin sodium mediated oxygen consumption, photodegradation, and photocytotoxicity which were observed with pulse energy densities increasing from 0.5 to 10 mJ/cm2. This result could be mainly attributed to absorption saturation. On the other hand, Porfimer sodium did not display significant absorption saturation with the pulse energy densities ranging from 0.31 to 31 mJ/cm2. The photodegradation mechanism for Porfimer sodium changed at high pulse energy density. This phenomenon might accelerate the photodegradation and cause the photocytotoxicity suppression.