Oyster aquaculture is flourishing in the US and internationally, delivering wide-ranging benefits to coastal communities, economies, and ecosystems. While the oyster aquaculture industry has grown substantially, a number of ongoing challenges limit industry growth. The issue of biofouling is paramount among these impediments to industry growth and farmers employ a range of techniques for biofouling control, including chemical immersion, physical methods, paints or coatings, and biological control methods. Desiccation, or the periodic aerial exposure of oysters and cages, is a popular biofouling control strategy and previous research has demonstrated the effectiveness of 24 consecutive hours of desiccation at a weekly frequency (compared to 24 hours bi-weekly, monthly, or seasonally), but this treatment has yielded a growth penalty in addition to biofouling control. The optimal interval (duration) of desiccation has not been thoroughly investigated and shorter intervals applied at a weekly frequency may yield different results. Therefore, this dissertation set out to investigate the effects of multiple weekly desiccation intervals (0-, 4-, 8-, and 24-hours) on eastern oyster (Crassostrea virginica) production and biofouling control. In Chapter 2, I examined responses of the biofouling community and oysters to three weekly desiccation intervals (0-, 8-, and 24-hours) at three commercial oyster farms in the Chesapeake Bay over 4 months. In Chapter 3, I conducted longer term (7 month) monitoring of the response of the biofouling community and oysters to four weekly desiccation intervals (0-, 4-, 8-, and 24-hours) at a single site in the Choptank River. In Chapter 4, I examined molecular (heat shock protein expression) and physiological (filtering rate, gametogenic stage, glycogen content) responses of oysters to four weekly desiccation intervals (0-, 4-, 8-, and 24-hours) in the Choptank River over 3 months. Results indicate broad-scale effectiveness of all desiccation treatments in reducing total biofouling coverage, although species- and site-specific responses were observed. Oyster growth was inconsistently affected by desiccation treatment, but reduced growth was observed in the 8- and 24-hour treatments in two of the three years of field investigations, perhaps influenced by reduced time spent in the water feeding and a delay in the onset of filtering post-desiccation. However, the timing of the greatest reduction in growth rates with desiccation suggests that concomitant stress of desiccation plus gametogenesis may have elevated the oysters’ stress response (reduced growth). Indeed, gametogenic stage and glycogen content were influenced by desiccation interval and oysters in the 24-hour treatment were the most likely to spawn. A high-level stress response via the upregulation of heat shock proteins (HSPs) was absent in oysters from the 8- and 24-hour treatments, indicating depressed HSP expression (and cellular protection) among the most stressed oysters. Future research into the importance of environmental factors during desiccation (air temperature, wind, humidity, etc.) could yield useful information to allow oyster farmers to target desiccation during optimal conditions, potentially limiting oyster exposure time in order to minimize oyster stress. Fouling reduction was significant in all treatments (4-, 8-, and 24-hour) and most consistent in the longer (8- and 24-hour) treatments. Therefore, a tradeoff is present between biofouling control and yield. Farmers prioritizing minimal biofouling may opt to desiccate for 8 or 24 hours weekly, while farmers seeking to maximize growth rates and minimize oyster stress may opt to desiccate for 4 hours weekly. Individual farmers must consider their own preferences regarding suitability of this husbandry technique, but results suggest that desiccation is an effective approach to biofouling control and can be applied with minimal stress to the oysters.