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The increase in greenhouse gasses (GHG) anthropogenic emissions and deforestation over the last decades have led to many chemical and physical changes in the climate system, affecting the atmosphere’s energy and water balance. A process that could be affected is the Amazonian moisture transport in the South American continent (including La Plata basin), which is crucial to the southeast Brazilian water regime. The focus of our research is on evaluating how local (i.e. Amazon deforestation) and global forcings (increase of atmospheric GHG concentration) may modify this moisture transport under climate change scenarios. We used two coupled land-atmosphere models forced by CMIP6 sea surface temperatures to simulate these processes for two scenarios: i) increase in carbon dioxide (CO2) RCP8.5 atmospheric levels (00DEF), and ii) total Amazon deforestation simultaneous with atmospheric CO2 levels increased (100DEF). These scenarios were compared with a control simulation, set with a constant CO2 of 388 ppm and present-day Amazon Forest cover. The 30-year Specific Warming Level 2 (SWL2) index evaluated from the simulations is set to be reached 2 years earlier due to Amazon deforestation. A reduction in precipitation was observed in the Amazon basin (−3.1 mm·day−1) as well as in La Plata Basin (−0.5 mm·day−1) due to reductions in the Amazon evapotranspiration (−0.9 mm·day−1) through a stomatal conductance decrease (00DEF) and land cover change (100DEF). In addition, the income moisture transport decreased (22 %) in the northern La Plata basin in both scenarios and model experiments. Our results indicated a worse scenario than previously found in the region. Both Amazon and La Plata hydrological regimes are connected (moisture and energy transport), indicating that a large-scale Amazon deforestation will have additional climate, economic and social implications for South America.