In recent decades, increasing human pressure has caused the gradual deterioration of the physical and chemical properties of water and soil. Salinity is an important factor influencing the quality of water. The aim of this comprehensive research was to determine the effect of increasing concentrations of sodium chloride, which is a salinity inducer, on the yield, photosynthesis efficiency (expressed with chlorophyll fluorescence measurement) and content of selected nutrients in the leaves of hydroponically grown lettuce (Lactuca sativa L.). Experiments were conducted at the following concentrations of NaCl: 0 (control treatment), 10, 20, 40, and 60 mmol L−1. Studies were conducted in two independent seasons: spring and autumn. The plants exposed to NaCl stress modified their chemical composition by lowering the uptake of (for 60 mmol L−1 NaCl in relation to control): N (−11%), K (−35.7%), and Mg (−24.5%), while increasing the sodium content (+2400%). The Na:K ratio was significantly narrowed (from 76:1 to 2.6:1). The increase in the Cl level in the lettuce leaves may also have caused a decrease in the content of nitrates. As a result of disturbed ionic balance, the RWC was significantly reduced (−6.2%). As a result of these changes, the yield of the biomass of the aerial parts decreased (more than two-fold for the highest NaCl concentration in relation to control) whereas the dry matter content increased (+32%). The measurement of fluorescence showed significant changes at the PSII level. Salinity modified the energy flow rate (F0, FM, FV, FV/FM) as well as the specific energy flows through the reaction centre (ABS/RC, TR0/RC, ET0/RC, DI0/RC). The PSII functioning index, calculated on the basis of energy absorption (PIAbs), also changed. The salinity induced with NaCl significantly worsened the physiological reactions of the plants in the PSII, changed the ionic balance, which resulted in a significantly lower yield of the plants. Due to increasing water quality problems, it will be necessary to use, in agriculture on a much larger scale than before, saline water treatment systems (e.g., highly effective nanofiltration and/or reverse osmosis).