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The lower Zarafshan region is considered as environmentally-vulnerable region for the Aral Sea crisis, climate change, pollution of surface and underground water resources, land degradation, and desertification processes that require sustainable development in a single geographic area in harmony with nature and society. Global climate change has changed the region's climate and negatively affects the natural ecosystems and the health of the population, and natural adaptation processes for these changes in the future are going to be extremely difficult. Today, the state, public organizations, ministries, research and higher education institutions concerned with the protection of the environment face the issue of identification, evaluation, and application of indicators ensuring the sustainable development of the country and its zones (regions). In this monograph, water, soil, biodiversity, atmospheric air and socio-economic indicators for sustainable development in the Lower Zarafshan region were identified and evaluated on the basis of long-term observations, analyzes and statistical data processing.