Carbon fixation has a central role in determining cellular redox poise, increasingly understood to be a key parameter in cyanobacterial physiology. In the cyanobacterium Prochlorococcus-the most abundant phototroph in the oligotrophic oceans-the carbon-concentrating mechanism is reduced to the bare essentials. Given the ability of Prochlorococcus populations to grow under a wide range of oxygen concentrations in the ocean, we wondered how carbon and oxygen physiology intersect in this minimal phototroph. Thus, we examined how CO2:O2 gas balance influenced growth and chlorophyll fluorescence in Prochlorococcus strain MED4. Under O2 limitation, per-cell chlorophyll fluorescence fell at all CO2 levels, but still permitted substantial growth at moderate and high CO2. Under CO2 limitation, we observed little growth at any O2 level, although per-cell chlorophyll fluorescence fell less sharply when O2 was available. We explored this pattern further by monitoring genome-wide transcription in cells shocked with acute limitation of CO2, O2 or both. O2 limitation produced much smaller transcriptional changes than the broad suppression seen under CO2 limitation and CO2/O2 co-limitation. Strikingly, both CO2 limitation conditions initially evoked a transcriptional response that resembled the pattern previously seen in high-light stress, but at later timepoints we observed O2-dependent recovery of photosynthesis-related transcripts. These results suggest that oxygen has a protective role in Prochlorococcus when carbon fixation is not a sufficient sink for light energy.