Sugars, produced through photosynthesis, are at the core of all organic compounds synthesized and used for plant growth and response to the environmental changes. Therefore, their production, transport and utilization is highly regulated and integrated throughout the plant life cycle. The maintenance of sugar partitioning between the different subcellular compartments (e.g., cytosol, vacuole, chloroplast), and mediated by different families of sugar transporters (e.g., SUC/SUT, SWEET, ERDL), is instrumental to adjust the photosynthesis performance and response to abiotic constraints. Here we investigated in Arabidopsis the consequences of the disruption of four genes coding for SWEET sugar transporters (SWEET11, SWEET12, SWEET16 and SWEET17) on plant photosynthesis and response to drought. Our results show that, the disruption of the intercellular sugar transport, mediated by SWEET11, negatively impacts photosynthesis efficiency and net CO2 assimilation while the stomatal conductance and transpiration are increased. These defects are accompanied by an impairment of both cytosolic and chloroplastic glycolysis leading to an accumulation of soluble sugars, starch and organic acids. Further, our results suggest that in the swt11swt12 mutant, the sucrose-induced feedback mechanism on stomatal closure is poorly efficient. On the other hand, changes in fructose partitioning in mesophyll and vascular cells, mediated by SWEET17, positively impact photosynthesis probably through an increased starch synthesis together with a higher vacuolar sugar storage. Finally, our work shows that, a fine tuning, at transcriptional and/or translational levels, of the expression of SWEET11, SWEET16 and SWEET17 is needed in order to properly respond to drought stress.