The Sydney rock oyster (SRO; Saccostrea glomerata) is the most intensively cultivated oyster species in Australia. However, SRO cultivation has been impacted by a number of diseases, including Queensland unknown disease (QX disease) which regularly causes severe mortalities in a number of Australian estuaries. The infectious aetiological agent of QX disease is the Marteilia sydneyi parasite, although this disease is multi-factorial with a number of environmental and host factors contributing to disease dynamics. To date, the most successful strategy to combat QX disease has been breeding disease resistant oysters, which appear to improve immunity against the disease. Despite this, the mechanisms that drive QX resistance in these oysters is not fully understood. One potential factor that could influence disease resistance is the microbiome. To determine the influence of location, season and disease-resistance on the SRO microbiome, we used 16S rRNA amplicon sequencing. The microbiomes of six SRO families categorized as QX resistant and QX susceptible, deployed to two different locations (Port Stephens and Wallis Lake, NSW, Australia) and over two sampling time points (Austral summer and winter) were characterized. The SRO microbiomes was significantly influenced by location and season, while disease-resistance was only found to influence the microbiome at the winter-time point. This finding indicates that while host genetics plays a role in influencing the microbiome structure, seasonal environmental parameters may override its influence.