Oxygen-18 and deuterium analyses of water samples are provided from a regional survey of lakes, wetlands, soil waters, groundwaters, and snowpack samples collected in the Southern Athabasca Oil Sands (SAOS) region, Alberta, Canada, mainly during 2007–2009. Lake, wetland, and river sampling were conducted by helicopter during late summer, capturing conditions close to peak evaporative enrichment. Shallow soil water from the unsaturated zone was also collected in late summer, whereas deeper groundwaters from Quaternary aquifers, Quaternary channels, and uppermost Cretaceous strata, were collected primarily as part of winter drilling programs by industrial partners. Snowpack samples were collected in late March/early April, prior to significant spring melt. This dataset includes 1576 isotopic analyses made on 788 water samples as well as selected isotope mass balance model outputs (lake evaporation/inflow and water yield to lakes). These basic model data are provided to facilitate evaluation of the method as a tool for spatial mapping of water yield and its interannual variability. Details and further discussion on the isotope mass balance approach are provided in “Mapping water yield distribution across the southern Athabasca Oil Sands area: baseline surveys applying isotope mass balance of lakes” (Gibson et al., 2019). Overall, the data are expected to be useful, in comparison with local and regional datasets, for water resource management and planning, including design of monitoring networks and environmental impact assessments for oil sands projects.