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Groundwater is a main source of drinking water for some rural areas. People in these rural areas are potentially at risk from elevated levels of arsenic (As) due to a lack of water treatment facilities. The objectives of this study were to (1) measure As concentrations in approximately 50 groundwater samples from rural domestic wells in the western United States, (2) explore the potential of cupric oxide (CuO) particles in removal of As from groundwater samples under natural conditions (i.e., without adding competing anions and adjusting the pH or oxidation state), and (3) determine the effects of As removal on the chemistry of groundwater samples. Forty-six groundwater well samples from rural domestic areas were tested in this study. More than 50% of these samples exceeded the U.S. Environmental Protection Agency Maximum Contaminant Limit (US EPA MCL) of 10 µg/L for As. CuO particles effectively removed As from groundwater samples across a wide range of pH (7.11 and 8.95) and concentrations of competing anions including phosphate (<0.05 to 3.06 mg/L), silica (<1 to 54.5 mg/L), and sulfate (1.3 to 735 mg/L). Removal of As showed minor effects on the chemistry of groundwater samples, therefore most of the water quality parameters remained within the US EPA MCLs. Overall, results of this study could help develop a simple one-step process to remove As from groundwater.