Recently, beneficial elements have received much attention because of their pivotal contribution in crop sustainability. The biofortification of plants with these elements is one of the brilliant strategies that provide these elements in the food chain for human consumption. Additionally, an unprecedented approach has been made to study the impact of the beneficial elements on plant growth, development, yield, and quality. Accordingly, this study was conducted to investigate the separate efficacy of the cobalt, selenium, and silicon on the biofortification of lettuce cv. Limor plants and scrutinize their potential impacts on growth and productivity during the 2020 and 2021 seasons. Ten foliar treatments, including cobalt sulphate at 100, 200 and 300 μM, sodium selenite at 10, 20 and 30 μM, and sodium silicate at 0.5, 1 and 2 mM, and distilled water as a control treatment. The experimental design was a completely randomized block with three replicates. Results clarified that the spraying of these beneficial elements significantly enhanced the vegetative growth parameters, mineral content, chlorophyll content, sugars and free amino acids as compared to the control. The treatments did not affect the content of nitrate and nitrite in the lettuce heads. The increases in head fresh weight ranged from 11.35 to 14.54% in the first season, and from 13.07 to 16.95% in the second season. In conclusion, supplying cobalt sulphate at 100 μM, sodium selenite at 20 μM or sodium silicate at 2 mM as foliar sprayings not only improves the vegetative growth and yield of lettuce plants but also enhances the nutritional quality of plants and fortifies the content of these elements in the lettuce heads.