In recent years, the interest on baby-leaf lettuce has grown steadily, because it is richer in bioactive compounds than other traditional vegetables. However, the quality of lettuce is being increasingly affected by climate change. It is very rare for a climatic effect to occur in isolation. Even then, a large body of work has only focused on the effect of isolated heat stress, fertilization, and elevated CO2, on morphological, physiological and biochemical parameters. Thus, very few works have focused on how the combination of several of these factors can affect these parameters. For first time, the present work studied the combined effect derived from the application of two different levels of CO2 (400 and 1000 ppm of CO2), four different NO3-/ NH4+ ratios (100/0 (T-I), 100/0 before the short-term heat stress and finally without NO3- (T-II), 80/20 (T-III) and 50/50 (T-IV)), and a short-term heat stress (25 and 43°C), on some physiological and quality parameters (dry biomass, photosynthetic parameters, pigments content, lipid peroxidation and total soluble proteins content) of baby-leaf lettuce cv Derbi. Additionally, a comparison of that combined effect of all these parameters between inner and outer leaves was also performed. The results obtained indicated that the interaction between the nutrient solution containing a 50/50 NO3-/ NH4+ ratio and a high concentration of CO2 (1000 ppm) improved the biomass, photosynthesis, intercellular/external CO2 concentration ratio (ci/ca), stomatal conductance (gs), evapotranspiration (E) and lipid peroxidation, and protein content in this baby-leaf lettuce. The results obtained in this work lead us to conclude that this existing interaction between the NO3-/ NH4+ ratio and the elevated CO2 concentration may be considered as a new strategy for making baby-leaf lettuce more resistant to heat stress, in other words, stronger against the ever more frequent heat waves.