Lettuce (Lactuca sativa L.) is one of the most popular leafy vegetables. There is a wide variety of types and cultivars that have different compounds with healthy benefits as polyphenols. These compounds are susceptible to variation among cultivars, growing practices, processing and storage conditions. Among environmental factors, salinity affects 3×106 km2 and 19.5% of agricultural land is considered saline, also each year 2 million ha become saline soils, harming agricultural production. High level of NaCl can be toxic for plants, however, plants have developed different mechanisms against oxidative stress generated by salt, such as accumulation of protective compounds, as antioxidants, that can eliminate the reactive oxygen species (ROS) and protect the cells. Lettuce is classified as a moderately salt tolerant culture, but there is not enough information about the effects of salinity on antioxidant compound concentration in different varieties and cultivars and its tolerance to a saline environment. So, the aim of this study was to evaluate the effect of salt on yield, phenolic compounds content and antioxidant capacity in two commercial lettuce cultivars: Lollo Bionda ‘Levistro’ and Lollo Rosso ‘Carmoli’. Both lettuce cultivars were grown in floating root hydroponic system using a nutrient solution with 0, 50 and 100 mM of NaCl. After 30 days of culture, young lettuces were harvested. Fresh weight and dry matter percentage were measured as yield parameters and total phenolic and antioxidant capacity were determined as polyphenols compounds estimation. After culture, both cultivars showed a decrease in fresh weight and an increase in dry matter percentage. Despite yield reduction, increased total phenolic compounds and antioxidant capacity were found in both cultivars.