Drinking water treatment plants throughout the world are increasingly facing the presence of toxic cyanobacteria in their source waters. During treatment, the oxidation of cyanobacteria changes cell morphology and can potentially lyse cells, releasing intracellular metabolites. In this study, a combination of techniques was applied to better understand the effect of oxidation with chlorine, ozone, potassium permanganate, and hydrogen peroxide on two cell cultures (Microcystis, Dolichospermum) in Lake Champlain water. The discrepancy observed between flow cytometry cell viability and cell count numbers was more pronounced for hydrogen peroxide and potassium permanganate than ozone and chlorine. Liquid chromatography with organic carbon and nitrogen detection was applied to monitor the changes in dissolved organic matter fractions following oxidation. Increases in the biopolymer fraction after oxidation with chlorine and ozone were attributed to the release of intracellular algal organic matter and/or fragmentation of the cell membrane. A novel technique, Enhanced Darkfield Microscopy with Hyperspectral Imaging, was applied to chlorinated and ozonated samples. Significant changes in the peak maxima and number of peaks were observed for the cell walls post-oxidation, but this effect was muted for the cell-bound material, which remained relatively unaltered.