The ability to acclimate to changing temperature has consequences for the biogeographic range of a species and their potential for surviving ocean warming. Using a tide simulator, which recreates tidal conditions by controlling water levels, water and air temperatures, light levels, and food availability, we explored how temperature and tidal zone (i.e. intertidal and subtidal) influences the abundance of sirtuin 5 (SIRT5) protein in a California native mussel (Mytilus californianus). We compared how gill tissue abundance of SIRT5, a key regulator of the cellular stress response and energy metabolism responded in M. californianus exposed to different temperature conditions (13, 16, 19 and 22°C) over a period of four weeks. Two SIRT5 isoforms, one a putative cytosolic form and the other a mitochondrial form were found to be expressed in mussel gill tissue. The mitochondrial isoform increased during acclimation to warm temperatures. This finding is the first to show how SIRT5 protein abundance changes with temperature acclimation. Surprisingly, we did not identify any differences in gill SIRT5 abundance between mussels from intertidal and subtidal locations. Our results suggest that characterizing the responses of SIRT isoforms may lead to a better understanding of the physiological diversity of sirtuins.