In order to investigate the water use efficiency and quantitative and qualitative indicators of three cucumber cultivars in different growing media with a closed hydroponic system, an experiment was conducted as a factorial in a randomized complete block design with 3 replications. The treatments included 3 types of growing substrate (cocopeat-perlite and sand (solid-based) and modified NFT (liquid-based)) and 3 greenhouse cucumber cultivars (Strong-Sun, Yalda, and RY). The vegetative, qualitative and physiological traits measured in this experiment included leaf number and area, stem diameter, chlorophyll a, b and total chlorophyll, photosynthesis, yield, soluble solids, EC and pH of fruit and water use efficiency. Based on the results, the highest leaf number was observed in the Strong Sun cultivar and the modified NFT and cocopeat-perlite substrates. Also, the highest leaf area was observed in the Strong Sun cultivar. The highest photosynthesis rate was observed in Strong Sun cultivar in cocopeat-perlite medium (12.41 µmol/m2.s) followed by Strong Sun and modified NFT medium. Also, the highest percentage of total dissolved solids was observed in Strong Sun cultivar in modified NFT and cocopeat-perlite medium. Based on the results, the highest water use efficiency was observed in Strong Sun cultivar and modified NFT medium (4.78 kg/m3) and the lowest in Yalda cultivar and sand medium (1.60 kg/m3). Based on the results, modified NFT medium (due to better management of water resources and nutrient solution) and Strong Sun cultivar are recommended for cultivation in greenhouse units with closed hydroponic systems.