Iron and light are recognized as limiting factors controlling Southern Ocean phytoplankton growth. Recent field-based evidence suggests, however, that manganese availability may also play a role. Here we examine the influence of iron and manganese on protein expression and physiology in
Phaeocystis antarctica
, a key Antarctic primary producer. We provide taxon-specific proteomic evidence to show that in-situ Southern Ocean
Phaeocystis
populations regularly experience stress due to combined low manganese and iron availability. In culture, combined low iron and manganese induce large-scale changes in the
Phaeocystis
proteome and result in reorganization of the photosynthetic apparatus. Natural
Phaeocystis
populations produce protein signatures indicating late-season manganese and iron stress, consistent with concurrently observed stimulation of chlorophyll production upon additions of manganese or iron. These results implicate manganese as an important driver of Southern Ocean productivity and demonstrate the utility of peptide mass spectrometry for identifying drivers of incomplete macronutrient consumption.