The present study investigated the effects of using arsenic (As) contaminated irrigation water in Lactuca sativa L. cropping. Two different arsenic concentrations, i.e., 25 and 85 μg L(-1) and two different soils, i.e., sandy and clay loam, were taken into account. We determined the arsenic mobility in the different soil fractions, its amount in groundwater, and the phytotoxicity and genotoxicity. Nuclear magnetic resonance (NMR) and inductively coupled plasma (ICP) were used to assess the lettuce metabolic profile changes and the arsenic uptake by the plant, respectively, as a function of the various conditions studied, i.e., As content and type of soil. Data indicated that at both concentrations in sandy soil, arsenic is in part quickly leached and thus present in groundwater and in part absorbed by the vegetable, being therefore readily available for assimilation by consumption. NMR results reported a large modification of the metabolic pattern, which was depending on the pollutant amount. In clay loam soil, the groundwater had a low As content with respect to sandy soil, and NMR and ICP performed on the lettuce did not reveal severe changes related to As, most likely because the metalloid is bound to the colloidal fraction.