Light is an important tool in chemical biology and is often applied to investigate protein function in a complex biological system due to its high level of spatiotemporal control. Methods of optical protein activation exist, however, the deactivation of proteins using light is less common. Chromophore-assisted light inactivation (CALI) is a method of optical protein modulation that relies on a photosensitizer that generates reactive oxygen species when irradiated with a specific wavelength of light. This can result in the oxidation of the protein of interest and eventual removal of activity. Here, I describe a method of optical deactivation of the beta-lactamase enzyme, OXA-48 through the covalent delivery of three different photosensitizers using amine-reactive N-hydroxysuccinimide or isothiocyanate-activated small molecules. Through this work, I have demonstrated efficient labeling of the protein of interest and optical deactivation upon light irradiation of photosensitizer-labeled proteins.