Lettuce, a major food crop within the European Union and the most used for the so-called 'Fourth Range' of vegetables, can associate with arbuscular mycorrhizal fungi (AMF). Mycorrhizal symbiosis can stimulate the synthesis of secondary metabolites, which may increase plant tolerance to stresses and enhance the accumulation of antioxidant compounds potentially beneficial to human health. Our objectives were to assess (1) if the application of a commercial formulation of AMF benefited growth of lettuce under different types and degrees of water deficits; (2) if water restrictions affected the nutritional quality of lettuce; and (3) if AMF improved the quality of lettuce when plants grew under reduced irrigation. Two cultivars of lettuce consumed as salads, Batavia Rubia Munguía and Maravilla de Verano, were used in the study. Four different water regimes were applied to both non-mycorrhizal and mycorrhizal plants: optimal irrigation (field capacity [FC]), a water regime equivalent to 2/3 of FC, a water regime equivalent to 1/2 of FC and a cyclic drought (CD). Results showed that mycorrhizal symbiosis improved the accumulation of antioxidant compounds, mainly carotenoids and anthocyanins, and to a lesser extent chlorophylls and phenolics, in leaves of lettuce. These enhancements were higher under water deficit than under optimal irrigation. Moreover, shoot biomass in mycorrhizal lettuces subjected to 2/3 of FC were similar to those of non-mycorrhizal plants cultivated under well-watered conditions. In addition, lettuces subjected to 2/3 FC had similar leaf RWC than their respective well-watered controls, regardless of mycorrhizal inoculation. Therefore, results suggest that mycorrhizal symbiosis can improve quality of lettuce and may allow restrict irrigation without reducing production.