In situ viability of oceanic phytoplankton may be relatively low in open oceans. This is assumed to be related to the high-irradiance and low-nutrient conditions typical for oligotrophic regions. However, experimental evidence for this phenomenon was not yet available. In the present study, the importance of nutrient availability in high-irradiance–induced viability loss was therefore studied for three key oceanic phytoplankton species. Prochlorococcus marinus, Ostreococcus sp., and Thalassiosira oceanica were acclimated to two different N : P ratios. Growth, viability, and photophysiology were assessed under nutrient-replete and N- and P-starved conditions. Simultaneously, high-irradiance–induced photoinhibition and viability loss were measured and three inhibitors were used to investigate the underlying physiological mechanisms contributing to viability loss. High-irradiance exposure caused viability loss in P. marinus and Ostreococcus sp., but not in T. oceanica. Low-nutrient availability enhanced survival during high-irradiance exposure, although species-specific differences were observed. The lower sensitivity to high-irradiance intensities at low-nutrient availability was related to conformational changes in photosystem II in P. marinus, to enhanced photoprotection by the xanthophyll pigment cycle and alternative electron transport in Ostreococcus sp., and to enhanced photoprotection by the xanthophyll pigment cycle in T. oceanica. Climate change may lead to enhanced stratification in the open ocean. The resulting increase in the average irradiance intensity phytoplankton experience may promote viability loss in the smallest phytoplankton size fraction. However, this effect may partially be counteracted by the simultaneously expected decrease in nutrient availability.