This paper considers the interpretation of uranium (U) ore–mineral equilibrium calculations in groundwater to help understand ore genesis and assist exploration. Groundwater samples collected on two recent field sampling trips in the Frome Embayment region of South Australia have been analysed for major and selected trace elements. These data together with previous published data have been used to construct geochemical models of the equilibrium state of the groundwaters. Species’ activities and mineral saturation states have been estimated. Calculated species’ activities are generally in the range reported in the previous modelling by Giblin involving groundwaters from similar local sources. Our models indicate that amorphous UO2, rather than the ore minerals coffinite and uraninite, is the solidU mineral phase that is the likely control on groundwater U concentration. The UO2(am) saturation index did not show a systematic variation with ore grade or proximity to mineralization. Its use for exploration at smaller scales, where the groundwater composition is similar between sample sites and U minerals are present at various concentrations, is doubtful. Inherent limitations on the information provided by mineral saturation indices restrict their exploration application,particularly in high salinity palaeochannel groundwater environments, such as those common in Australia.