Biofouling poses a major challenge to the growing US oyster aquaculture industry and periodic desiccation is a popular husbandry technique for biofouling control. However, desiccation is also associated with reduced oyster growth and elevated mortality, and the duration of desiccation can influence the magnitude of oyster stress response. A clearer understanding of the physiological responses of oysters to desiccation will help to refine desiccation as a husbandry technique. In this study, we measured growth, clearance rates, gametogenic stage, glycogen concentration, and the expression of heat shock proteins (HSPs) among diploid Crassostrea virginica desiccated for 0, 4, 8, or 24 hours per week over a three-month period (July – September 2020) in the Choptank River, MD. Oyster clearance rate was reduced immediately after re-submergence in the 8- and 24-hour treatments during the August sampling, but the clearance reduction did not persist after a 4-day re-submergence period or in September (Figure 1). Glycogen content and gonad development demonstrated an expected inverse relationship in July where oysters in the 0-hour treatment had more developed gonad and reduced glycogen, and oysters in the 4-, 8-, and 24-hour treatments had less developed gonad and more glycogen, but these relationships were not present in August. Oysters’ expression of HSPs lacked clear treatment effects but trends suggested greater expression during August compared to July in the 0- and 4-hour treatments, while oysters in the 8- and 24-hour treatments mounted a low expression of inducible HSPs during both the July and August samplings. Overall, the 4-hour desiccation interval resulted in less stress to oysters, although the stress response of oysters in the longer desiccation treatments (8- and 24-hour) varied over time. Based on these results, desiccation for 4 hours weekly may be a suitable husbandry tactic with little likelihood of elevated oyster stress.