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The effects of climate change, including ocean acidification and ocean heatwaves, on biological communities in estuaries are often uncertain. Part of the uncertainty is due to the complex suite of environmental factors in addition to acidification and warming that influence the growth of shells and skeletons of many estuarine organisms. The goal of this study was to document spatial and temporal variation in water column properties and to measure the in situ effects on larval and recently settled stages of ecologically important Olympia oysters (Ostrea lurida) and commercially important Pacific oysters (Crassostrea gigas) in a low-inflow estuary with a Mediterranean climate in Northern California. Our results reveal that seasonal inputs of upwelled or riverine water create important and predictable gradients of carbonate system parameters, temperature, salinity, dissolved oxygen (DO), and other variables that influence oyster performance, and that the influence of these gradients is contingent upon the location in the estuary as well as seasonal timing. During upwelling events (dry season), temperature, carbonate chemistry, and DO had the greatest impact on oyster performance. During runoff events (wet season), gradients in salinity, nutrient concentrations, and total alkalinity driven by river discharge were comparatively more important. These results suggest that the spatial importance of carbonate chemistry and temperature are seasonally variable and are two of several other factors that determine oyster performance. We use these results to discuss future impacts on oysters given projected regional changes in the frequency and magnitude of upwelling and precipitation-driven runoff events.