Indoor crop cultivation systems such as vertical farms or plant factories necessitate artificial lighting. Light spectral quality can affect plant growth and metabolism and, consequently, the amount of biomass produced and the value of the produce. Conflicting results on the effects of light spectrum in different plant species and cultivars make it critical to implement a singular lighting solution. In this study we explored the response of green and red leaf lettuce cultivars (’Aquino’, CVg, or ‘Barlach’, CVr, respectively) to long-term blue-enriched light application (WB). Plants were grown for 30 days in a growth chamber with optimal environmental condi-tions (temperature: 20°C, relative humidity: 60%, ambient CO2, Photon Flux Density (PFD) of 260 µmol m-2 s-1 over an 18-h photoperiod). At 15 days after sowing (DAS) white spectrum LEDs (WW) were compared to WB (λPeak = 423 nm) maintaining the same PFD of 260 µmol m-2 s-1. At 30 DAS, both lettuce cultivars resulted adapted to the blue light variant, though the adaptive re-sponse was specific to the variety. Rosette weight, light use efficiency and maximum operating efficiency of PSII photochemistry in the light, Fv/Fm’, were comparable between the two light treatments. Significant light quality effect was detected on stomatal density and conductance (20% and 17% increase under WB, respectively, in CVg) and, on the modified anthocyanin re-flectance index (mARI) (40% increase under WB, in CVr). Net photosynthesis response was gen-erally stronger in CVg compared to CVr; e.g. net photosynthetic rate, Pn, at 1000 µmol m-2 s-1 PPFD increased from WW to WB by 23% in CVg, compared to 18% in CVr. Results obtained suggest the occurrence of distinct physiological adaptive strategies in green and red pigmented lettuce cultivars to adapt to the higher proportion of blue light environment.