Hydroponic systems have the potential for being one of the most promising sustainable alternative methods of food production, where they confer the advantages of producing higher yields with better control over plant growth. The main purpose of this study is to determine differences in growth rates, sensory attributes and nutrient uptake upon growing lettuce (Lactuca sativa L.) in various hydroponic subsystems at two different plant spacings. We investigated the interaction of different effects on lettuce growth in four hydroponic subsystems, Deep Water Culture ((DWC), Nutrient Film Technique (NFT), Media- Bed system (MB) and Sandponic (SP), at two different plant densities, at narrow planting spacings (20 x25 cm), and larger planting spacings (24 x 25 cm). Our findings show that cultivation methods and planting spacing greatly influence lettuce growth. Overall, the present study provides direct evidence that DWC and NFTs subsystems at both planting spacings performed the best in terms of giving higher yield production, higher plant growth parameters, and better sensory attributes compared to other cultivation systems. Lettuces grown in the DWC system had higher chlorophyll B (29.13 ± 0.82 mg/100 g), and carotene content (32.40 ± 1.27 mg/100 g) in narrow planting spacing and were the most preferred lettuces according to taste tests (52.4%).