Hypoxia is an emerging concern in coastal ecosystems worldwide, and the number of areas experiencing hypoxia has increased exponentially in recent years. It is most prevalent in summer months when elevated temperatures lead to increased oxygen consumption by resident biota, reduced oxygen solubility in sea water, and limited ventilation of these waters. In the face of a warming climate, there is uncertainty in how hypoxia will influence estuarine microbiota, especially in regards to opportunistic bacterial pathogens, and their impact on host species. The frequency at which they experience hypoxia, combined with the lack of understanding as to which factors are required for virulence, make Vibrio species an ideal model for studying hypoxia. The goals of this dissertation were to explore both the ecophysiology of the opportunistic human pathogen, V. vulnificus, and the host-pathogen interactions of V. coralliilyticus and the Eastern oyster Crassostrea virginica. Utilizing a variety of phenotypic, molecular, and next-generation sequencing techniques these studies have revealed a distinct response to both in vitro and in situ hypoxia. Furthermore, these studies allowed us to characterize the different responses of clinical and environmental genotypes of V. vulnificus, which has revealed important mechanisms for environmental maintenance and virulence. Additionally, these studies allowed us to describe the mechanisms that facilitated the rapid mortality in oysters exposed to hypoxia and V. coralliilyticus. Collectively, this dissertation contributes greatly to our understanding of hypoxia on representative Vibrio species, which has implications for both human and ocean health.