Giant clams are found living in nutrient-poor seawaters where light is adequately available due to their mutualistic association with phototrophic dinoflagellates of the family Symbiodiniaceae. These symbiotic dinoflagellates also known as zooxanthellae are found inside a zooxanthellal-tubule system mainly in the colorful and extensible outer mantle. The outer mantle uniquely possesses iridocytes that absorb harmful ultraviolet radiation and deflect light of wavelength conducive for photosynthesis to the symbionts. The iridocytes can also back-reflect light of other wavelengths engendering multiple color patterns to the outer mantle. They possess a mechanism which involves vacuolar-type H+-ATPase (ATP6V1), to facilitate the transfer of carbon dioxide from the host to the symbionts for photosynthesis. They are therefore strongly ATP6V1 subunit A (ATP6V1A)-immunopositive. Global warming leads to rising seawater temperatures can result in the loss of symbionts, depletion of symbiont’s pigments and/or host’s pigments in the outer mantle of giant clams or bleaching. The outer mantle of Tridacna squamosa, showed a reduction in its brownish hue when exposed to an elevated temperature of 31 °C for 57 days as compared to that of the control kept at 26 °C. There was a drastic loss of 34% of symbionts quantities from the outer mantle after T. squamosa were exposed to 31 °C for 15 days followed by another 27% loss after exposure to 31 °C for 30 days. Thereafter, the symbionts quantities levelled off at 1.7 ´ 107 with no further loss observed on 57 days at 31 °C. Interestingly, the total chlorophyll content (expressed as per g outer mantle) did not decrease after T. squamosa were exposed to 31 °C for 15 days. It only decreased after T. squamosa were exposed to 31 °C for 30 days and 57 days. However, when the chlorophyll content was expressed as per symbiont, there was an increase in synthesis of chlorophyll by the symbionts when T. squamosa were exposed to 31 °C. The transcript level and protein abundance of symbiont-derived form II ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) decreased significantly in the outer mantle after exposure to 31 °C for 15, 30 and 57 days. The decrease in phototrophic potential could probably be due to the instability of RuBisCo at 31 °C. The ATP6V1A protein abundance in the outer mantle decreased significantly as compared to that of the control after T. squamosa were exposed to 31 °C for 57 days. Additionally, immunofluorescence microscopy confirmed the reduction in both iridocyte and symbiont populations. Thus, there was a reduction in the capacity of the iridocyte to transfer carbon dioxide to the symbionts for photosynthesis. The transcript levels and protein abundance of host’s copper-zinc- (CuZn) and manganese- (Mn) superoxide dismutase (SOD) in the outer mantle were also measured to assess oxidative stress occurring at 31 °C. There was a significant increase in the protein abundance of CuZnSOD but not MnSOD after T. squamosa were exposed to 31 °C for 15 days. Taken together, there could have been an increase in reactive oxygen species production, leading to the drastic loss of symbionts after T. squamosa were exposed to 31 °C for 15 days. The remaining symbionts were able to adapt to 31 °C after 30 days of exposure. These findings signify the importance of elucidating the effects of elevated temperature on both the symbionts and the host in order to fully understand the process of temperature-induced bleaching in giant clams.