Global warming may detrimentally affect symbiosis between dinoflagellates and other marine invertebrates. Heat stress has been found to induce cellular changes possibly via epigenetic modifications, including DNA methylation. In this project, we exposed symbiotic dinoflagellates to hyper-thermal conditions (+7°C) in the presence of a DNA methylation inhibitor, the drug 5-AZA-2’-deoxycytidine (5-AZA). We monitored the early signs of oxidative stress and physiological changes in dinoflagellates cultures in vitro. Real-time analyses of the production of reactive oxygen species (ROS) and antioxidant, reduced glutathione (GSH) were performed in living dinoflagellate cells using flow cytometry. After 24h of thermal stress, a 34% reduction in the algal density was noted only in the presence of DNA methylation inhibitor, while the opposite trend was reported in the cultures without 5-AZA, with a 33% increase in cell numbers. Our results revealed the negative effect of DNA methylation inhibitor drug on Symbiodiniaceae density and the size of cells when exposed to rising temperatures indicating the importance of DNA methylation for symbiotic dinoflagellates response to heat stress. Consequently, the plasticity of algal symbionts to adapt and survive in a thermally challenging marine environment may partially be influenced by DNA methylation.