Protein metabolism is an expensive cellular process that can generally account for one third of basal metabolism in animals. Shifts in the stability of proteins under increased environmental temperatures could potentially alter the energy budget of an organism. However, studying the thermal stability kinetics of individual proteins is tedious and ultimately, difficult to relate to changes in the fitness of an organism. Yet understanding how organisms inhabiting extreme environments (polar seas, hydrothermal vents, and deep ocean basins) are able to maintain or limit the rate of protein turnover in the total cellular protein pool is crucial for our understanding of the total metabolic costs associated with survival in these habitats. To assess protein stability in field collected organisms at a proteome scale, we developed a high-throughput assay for protein denaturation profiles of total tissue extracts in bivalves. These profiles are quantitative and reveal unique compositional features of different tissues. Heat stress experiments in the clam Mercenaria mercenaria reveal that the protein pool of mantle and digestive mass tissues are more thermally stable after a short exposure to 35°C. This increase in stability could have large implications for the energy budget of M. mercenaria when exposed to high summer water temperatures. This methodology could readily be used to assess the stability and/or turnover potential of a variety of organisms experiencing extremes of both temperature and pressure.