High-pressure sodium (HPS) lighting is increasingly replaced by LED lighting in lettuce greenhouse cultivation. In contrast to HPS lighting, LEDs do not heat radiation. Therefore, the leaf temperature is significantly lower under LEDs. This raises the question of whether LED lighting has a positive impact on the reduction in water consumption during lettuce production. In this paper, we investigated this question and found that the water consumption of lettuce produced under LEDs was significantly lower (−15%) than under HPS without loss of yield. We also found that supplementary lighting increases the concentrations of caffeoylquinic acid, dicaffeoyltartaric acid, dicaffeoylquinic acid and that of the total phenolic compounds in lettuce leaves by 61%, 39%, 163% and 38%, respectively. Only the LED fixture was also efficient enough to increase the concentration of caffeoyltartaric acid (+24%). Most of the phenolic compounds showed a very strong positive correlation with the chlorophyll concentration in lettuce, which predominated in the leaves exposed to the LED lighting. Based on these facts, we conclude that by optimizing the light composition, more sustainable plant production, higher concentrations of chlorophyll and some phenolic compounds are possible.