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Due to its high efficacy as a wide-spectrum disinfectant and its potential for the degradation of pollutants and pesticides, ozone has broad application prospects in agricultural production. In this study, micro/nano bubble technology was applied to achieve a saturation state of bubble nutrient solution, including micro-nano oxygen (O 2 group) and micro-nano ozone (O 3 group) bubble nutrient solutions. The effects of these solutions on lettuce physiological indices as well as changes in the microbial community within the rhizosphere substrate were studied. The application of micro/nano (O 2 and O 3 ) bubble nutrient solutions to substrate-cultured lettuce plants increased the amount of dissolved oxygen in the nutrient solution, increased the lettuce yield, and elevated the net photosynthetic rate, conductance of H 2 O and intercellular carbon dioxide concentration of lettuce plants. Diversity analysis of the rhizosphere microbial community revealed that both the abundance and diversity of bacterial and fungal communities in the substrate increased after plant cultivation and decreased following treatment with micro/nanobubble nutrient solutions. RDA results showed that the microbial community in the S group was positively associated with EC, that in the CK and O 2 groups exhibited a positive correlation with SC, and that in the O 3 group displayed a positive correlation with CAT and POD. Overall, the implementation of micro/nanobubble generation technology in soilless substrates can effectively increase the lettuce growth and yield, and O 3 had a more pronounced effect on lettuce yield and quality and the microbial community structure in the substrate than O 2 . Our study would provide a reference and theoretical basis for developing sustainable and green technology for promoting lettuce production and can be a promising alternative to conventional methods for improving crop yields.