Iron availability limits primary production in >30% of the world’s oceans; hence phytoplankton have developed acclimation strategies. In particular, cyanobacteria express IsiA (iron-stress-induced) under iron stress, which can become the most abundant chl-binding protein in the cell. Within iron-limited oceanic regions with significant cyanobacterial biomass, IsiA may represent a significant fraction of the total chl. We spectroscopically measured the effective cross-section of the photosynthetic reaction center PSI (σPSI) in vivo and biochemically quantified the absolute abundance of PSI, PSII, and IsiA in the model cyanobacterium Synechocystis sp. PCC 6803. We demonstrate that accumulation of IsiA results in a ∼60% increase in σPSI, in agreement with the theoretical increase in cross-section based on the structure of the biochemically isolated IsiA-PSI supercomplex from cyanobacteria. Deriving a chl budget, we suggest that IsiA plays a primary role as a light-harvesting antenna for PSI. On progressive iron-stress in culture, IsiA continues to accumulate without a concomitant increase in σPSI, suggesting that there may be a secondary role for IsiA. In natural populations, the potential physiological significance of the uncoupled pool of IsiA remains to be established. However, the functional role as a PSI antenna suggests that a large fraction of IsiA-bound chl is directly involved in photosynthetic electron transport.