Report of UNICEF, 2009 has shown that region along Mekong River in Cambodia has arsenic (As) pollution in groundwater. The major cause of As pollution was attributed to natural process such as the dissolution of As-containing minerals and anthropogenic activities such as percolation of water from mining waste. Cambodia has been recorded a higher concentration of arsenic in groundwater of several provinces including Kandal, Kampong Cham, Prey Veng, Kratie, and Steung Treng. Some studies have pointed out that the presence of arsenic in this groundwater might source from Mekong River. For this reason, this study aims to assess the distribution of arsenic in river and sediment of the Mekong and Bassac River, Cambodia. The water sample was collected from the surface, middle and bottom of the river in Kratie, Kampong Cham, and Kandal Province. The water samples (n=45) were analyzed for the physical and chemicals quality including As and Iron. Same analysis of Sediment samples (n=11) from the River of Kandal Province were also assessed for the concentration. The study found that the arsenic content in water samples of the Mekong River, Cambodia ranged from 2.75 µg/L to 4.14 µg/L in Kratie and Kampong Cham Province. In Kandal Province, the high concentration ranged from 10.16 µg/L to 15.64 µg/L. The arsenic concentrations in water in Kratie and Kampong Cham Province were generally below the environmental standard of Sub Decree On Water Pollution Control, 1999. On the other hand, the arsenic concentration in water from the study site of Kandal Province was not in the permitted standard. Sediment sample contents arsenic is ranged from 1.05 mg/Kg to 1.70 mg/Kg. It was found a high concentration of arsenic in sediment and bottom water. The result has shown that a good correlation through some literatures point out a high concentration of As in the groundwater of Kandal Province. This could be a reason and source of the presence of a high concentration of arsenic in groundwater of Kandal province.