<p>Protected areas are vital for safeguarding biodiversity, ensuring water quality, and mitigating carbon emissions. However, despite their recognized importance, their specific role in the climate system at different spatial scales across South America, in the context of ongoing Amazonian deforestation, remains poorly understood. Therefore, the hypothesis that “Amazonian protected areas mitigate the impacts of deforestation at different spatial scales in South America” is formulated. The Eta regional climate model was used to evaluate the mitigation role and fragility of Amazonian protected areas (Indigenous Lands and Conservation Units) in the face of deforestation projected to 2050. Precipitation and temperature, among other complementary variables, were evaluated in tropical and subtropical South America. The results of this study clearly demonstrate the mitigating role of Amazonian protected areas on climate at local, regional, and continental scales. In the presence of deforestation in the Amazon, the intact forest cover inside protected areas has a beneficial impact on both temperature and precipitation at a regional scale, including on deforested non-protected lands near these legally protected spaces. At a local scale, there is also a beneficial effect on temperature, while at a continental scale, there is a beneficial effect on precipitation. However, even inside well-preserved protected areas, the results showed a reduction of precipitation due to deforestation in neighboring non-protected areas. Therefore, this study highlights the importance of protected areas in the Amazon region to the climate of South America, and also considers it important to curb deforestation in non-protected areas of the Amazon.</p> Graphical Abstract <p>The Eta regional climate model was used to assess the importance of Amazonian protected areas on the climate of South America. Future deforestation scenarios projected for 2050, with and without forest cover preserved within Indigenous Lands and Conservation Units in the Brazilian Amazon, were simulated. The results show a mitigating role of Amazonian protected areas on climate at local, regional, and continental scales. In other words, the well-preserved protected areas in the Brazilian Amazon have a mitigation effect on rainfall and temperature in this region. There is also a mitigation effect on rainfall over the subtropical region of South America. Within Amazonian protected areas, intact forest cover mitigates the temperature impacts of deforestation in neighboring non-protected areas, but rainfall within these legally protected spaces is negatively affected. This study emphasizes the importance of protected areas in the Amazon region for the climate of South America, while also stressing the need to curb deforestation in unprotected areas of this biome.</p>