Quantification of the contributions of river-influenced margins to regional CO2 fluxes is difficult due to the high degree of spatial and temporal variability in these regions. We describe an algorithm for assessment of surface water partial pressure of CO2 (pCO2) from MODIS imagery in the northern Gulf of Mexico. Principal component analysis and multiple regression were used to relate surface pCO2 to environmental variables (T, S, chlorophyll). Subsequent retrieval of corresponding products from MODIS-Aqua L1B data permitted the assessment of regional distributions of pCO2. An area of low pCO2 was evident in the vicinity of the Mississippi River delta, consistent with field observations. Regional surface air to sea fluxes of CO2 were estimated as 2.0–4.2 mmol C m−2 d−1.