Since industrialization global CO2 emissions have increased, and as a consequence oceanic pH is predicted to drop by 0.3–0.4 units before the end of the century – a process coined ‘ocean acidification’. Consequently, there is significant interest in how pH changes will affect the ocean's biota and integral processes. We investigated marine picoplankton (0.2–2 µm diameter) community response to predicted end of century CO2 concentrations, via a ‘high-CO2’ (∼ 750 ppm) large-volume (11 000 l) contained seawater mesocosm approach. We found little evidence of changes occurring in bacterial abundance or community composition due to elevated CO2 under both phytoplankton pre-bloom/bloom and post-bloom conditions. In contrast, significant differences were observed between treatments for a number of key picoeukaryote community members. These data suggested a key outcome of ocean acidification is a more rapid exploitation of elevated CO2 levels by photosynthetic picoeukaryotes. Thus, our study indicates the need for a more thorough understanding of picoeukaryote-mediated carbon flow within ocean acidification experiments, both in relation to picoplankton carbon sources, sinks and transfer to higher trophic levels.