Perfluorooctanoic acid (PFOA) is a typical persistent organic pollutant commonly detected in ecosystem. Insights into the risks of PFOA in crops, from the perspectives of food nutritional compositions, are sparse. In this study, the physiological responses to PFOA induced oxidative stress were investigated in lettuce (Lactuca sativa) leaves hydroponically exposed to 5 and 50 mug/L PFOA. The effects on photosynthesis and nutritional compositions were characterized. 35.1 and 316.7 ng/g dry weight PFOA were bio-accumulated in lettuce leaves under exposure to 5 and 50 mug/L PFOA, respectively. PFOA led to exposure-dependent over-generation of reactive oxidative species (ROS; H(2)O(2), 8.1%-38.7%; OH, 11.3%-26.4%; O(2)(-), 3.1%-22.8%) in leaves. Both non-enzymatic and enzymatic antioxidants were activated to scavenge ROS. Nevertheless, metabolomics results indicated some nutritional compositions in lettuce leaves were elevated by environmentally relevant concentrations of PFOA. Both primary metabolites, such as carbohydrates in the tricarboxylic acid cycle and amino acids, and secondary metabolites, such as bioactive (poly)phenol and alkaloid compounds, were significantly up-regulated. Leaf net photosynthetic rates were stimulated and intercellular CO(2) concentration was decreased. A thorough scheme on the interaction between PFOA and lettuce leaves was proposed as well, to enhance the understanding of PFOA risks in crops. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved.