The effect of ocean biological productivity on marine clouds is explored over a large phytoplankton bloom in the Southern Ocean with the use of remotely sensed data. Cloud droplet number concentration over the bloom was twice what it was away from the bloom, and cloud effective radius was reduced by 30%. The resulting change in the short-wave radiative flux at the top of the atmosphere was –15 watts per square meter, comparable to the aerosol indirect effect over highly polluted regions. This observed impact of phytoplankton on clouds is attributed to changes in the size distribution and chemical composition of cloud condensation nuclei. We propose that secondary organic aerosol, formed from the oxidation of phytoplankton-produced isoprene, can affect chemical composition of marine cloud condensation nuclei and influence cloud droplet number. Model simulations support this hypothesis, indicating that 100% of the observed changes in cloud properties can be attributed to the isoprene secondary organic aerosol.