This study assessed the implication of oxidative stress in the mortality of cells of Microcystis aeruginosa Kütz. Cultures grown at 25°C were exposed to 32°C, darkness, and hydrogen peroxide (0.5 mM) for 96 h. The cellular abundance, chl a concentration and content, maximum photochemical efficiency of PSII (Fv/Fm ratio), intracellular oxidative stress (determined with dihydrorhodamine 123 [DHR]), cell mortality (revealed by SYTOX-labeling of DNA), and activation of caspase 3–like proteins were assessed every 24 h. The presence of DNA degradation in cells of M. aeruginosa was also assessed using a terminal deoxynucletidyl transferase-mediated dUTP nick end labeling (TUNEL) assay at 96 h. Transferring cultures from 25°C to 32°C was generally beneficial to the cells. The cellular abundance and chl a concentration increased, and the mortality remained low (except for a transient burst at 72 h) as did the oxidative stress. In darkness, cells did not divide, and the Fv/Fm continuously decreased with time. The slow increase in intracellular oxidative stress coincided with the activation of caspase 3–like proteins and a 15% and 17% increase in mortality and TUNEL-positive cells, respectively. Exposure to hydrogen peroxide had the most detrimental effect on cells as growth ceased and the Fv/Fm declined to near zero in less than 24 h. The 2-fold increase in oxidative stress matched the activation of caspase 3–like proteins and a 40% and 37% increase in mortality and TUNEL-positive cells, respectively. These results demonstrate the implication of oxidative stress in the stress response and mortality of M. aeruginosa.