Irrigation with desalinated seawater (DSW) is a potential solution for addressing water scarcity in semiarid re-gions across the globe. However, this strategy may compromise the health of agricultural ecosystems due to the high content of phytotoxic elements (mainly boron, B) in this water. Here, a three-year experiment was carried to evaluate the response of the soil's physicochemical and microbiological properties, and plant physiology, to three irrigation water treatments (DSW; fresh water, FW; and their blend (1:1), BW) in the presence or not of organic amendments. Lemon trees (Citrus limon (L.) Burm. fil. cv. Eureka), with a higher sensitivity to B toxicity, and apricot trees (Prunus armeniaca L. cv. 'Bulida'), with a lower one, were used as model plants. Lemon trees irri-gated with BW and DSW showed a decline in net photosynthesis and stomatal conductance, and an accumulation of B in leaves that exceeded the toxicity threshold. These effects were stronger in amended soils. In soils culti-vated with lemon trees, DSW irrigation increased the water-soluble nitrogen content, the urease activity, and the activity and biomass of the microbial community, and shifted the microbial community structure as compared with the other water treatments. The soil microbial community responses were controlled by the addition of organic amendments. The irrigation of apricots with DSW did not negatively impact plant physiological pa-rameters but increased the soil microbial biomass, as in the case of the lemon tree-soil system. These results suggest that DSW irrigation increases soil microbial biomass in both crop-soil systems but harms the physio-logical status of the most sensitive crop. Our findings provide an initial approach to evaluate the response of the plant-soil system to DSW.