In Nebraska, a large number (>200) of shallow sand-point and cased wells completed in coarse alluvial sediments along rivers and lakes still are used to obtain drinking water for human consumption, even though construction of sand-point wells for consumptive uses has been banned since 1987. The quality of water from shallow domestic wells potentially vulnerable to seepage from septic systems was evaluated by analyzing for the presence of tracers and multiple isotopes. Samples were collected from 26 sand-point and perforated, cased domestic wells and were analyzed for bacteria, coliphages, nitrogen species, nitrogen and boron isotopes, dissolved organic carbon (DOC), prescription and nonprescription drugs, or organic waste water contaminants. At least 13 of the 26 domestic well samples showed some evidence of septic system effects based on the results of several tracers including DOC, coliphages, NH4+, NO3−, N2, δ15N[NO3−] and boron isotopes, and antibiotics and other drugs. Sand-point wells within 30 m of a septic system and <14 m deep in a shallow, thin aquifer had the most tracers detected and the highest values, indicating the greatest vulnerability to contamination from septic waste.