Synechococcus sp. strains CC9311, WH8102, and CC9605 were compared to investigate their response to oxidative stress. Fluorescence measurements, cell counts, and cell growth rates were compared for each strain exposed to a range of concentrations of an oxygen radical producing poison, methyl viologen, and an inhibitor of carotenoid biosynthesis, norflurazon. The methyl viologen induced expressions of genes coding for the putative antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase/peroxidase, were also compared. The order of highest to lowest sensitivity to oxidative stress induced in the cell cytoplasm is CC9311, WH8102, and CC9605. Conversely, CC9605 is more sensitive to oxidative stress induced in the thylakoid compartment than CC9311. CC9311 significantly up regulated the expression of genes coding for NiSOD and CuZnSOD, two enzymes required to destroy reactive oxygen species. WH8102 up regulated the expression of genes coding for NiSOD and GP, though not to a significant degree. CC9605 up regulated genes coding for NiSOD, CuZnSOD, and catalase/peroxidase to a greater extent than both CC9311 and WH8102. The resistance of CC9605 to oxidative stress may have been facilitated by a unique system of regulation. Overall, these strains of Synechococcus revealed differing responses to oxidative stress likely due to their adaptation to different marine ecosystems.