Mesocosm experiments have been fundamental to investigate the effects of elevated CO2 and ocean acidification (OA) on planktic communities. However, few of these experiments have been conducted using naturally nutrient-limited waters and/or considering the combined effects of OA and ocean warming (OW). Coccolithophores are a group of calcifying phytoplankton that can reach high abundances in the Mediterranean Sea, and whose responses to OA are modulated by temperature and nutrients. We present the results of the first land-based mesocosm experiment testing the effects of combined OA and OW on an oligotrophic Eastern Mediterranean coccolithophore community. Coccolithophore cell abundance drastically decreased under OW and combined OA and OW (greenhouse, GH) conditions. Emiliania huxleyi calcite mass decreased consistently only in the GH treatment; moreover, anomalous calcifications (i.e. coccolith malformations) were particularly common in the perturbed treatments, especially under OA. Overall, these data suggest that the projected increase in sea surface temperatures, including marine heatwaves, will cause rapid changes in Eastern Mediterranean coccolithophore communities, and that these effects will be exacerbated by OA.