The ocean is a source of isoprene to the atmosphere. Although their global estimates are relatively low compared with the terrestrial source, these emissions have an influence on atmospheric chemistry. The lack of knowledge about the sources and sinks of isoprene in the ocean has hitherto precluded a precise assessment of when and where these emissions might be significant. Here we use the general circulation and biogeochemistry model Nucleus for European Modelling of the Ocean, Pelagic Interaction Scheme for Carbon and Ecosystem Studies (NEMO-PISCES) to explore different parameterizations of the 3D oceanic sources and sinks of isoprene. In addition, we investigate a representation of the isoprene emission due to photoproduction in the sea surface microlayer. Our model estimates are complemented by a new data compilation of laboratory isoprene production rates and in situ isoprene concentrations. This study constitutes the first attempt to simulate isoprene in a global 3D ocean biogeochemical model. We find that sea surface temperature is an important driver modulating phytoplankton isoprene production and that light levels only play a secondary role at the scale of the global ocean. Furthermore, the use of a variable biochemical consumption rate improves the model-data comparison. We show the importance of isoprene production below the mixed layer and, as a consequence, demonstrate that models based on 2D surface satellite chlorophyll-a could miss up to 18.5% of oceanic isoprene emissions. The oceanic isoprene emissions to the atmosphere are estimated to 0.66 (0.43-0.82) Tg C yr −1 in the low range of previous estimates.