The concern about emerging contaminants such as pharmaceuticals is growing, mainly due to the increased global consumption of synthetic chemicals and the potential risk to environmental and human health. Although developing countries may be hotspots of pharmaceutical pollution, the knowledge about the occurrence of pharmaceuticals is still limited and patchy. Brazil holds one of the largest freshwater volumes globally, yet, little is known about the occurrence of pharmaceuticals in reservoirs although they make up key water sources. The aim of this study was, therefore, to investigate micropollutant occurrence, mainly pharmaceuticals, in four freshwater reservoirs distributed in Brazil. Water samples were collected in the Curuá-Una (CUN, Amazon region), Chapéu D’Uvas (CDU, Atlantic Forest region), Funil (FUN, Atlantic Forest region), and Simplício (SIM, Atlantic Forest region) reservoirs. The occurrence of 28 different micropollutants, including 26 pharmaceuticals, was investigated with target analysis on a UHPLC-Orbitrap-MS/MS, and a non-target screening approach was performed on all water samples to identify the presence of additional contaminants. The highest micropollutant concentrations were observed in FUN and SIM, which are the reservoirs with the largest population size in the catchment. Only caffeine was detected in CDU and CUN, which are reservoirs less influenced by urbanization. Metformin was the pharmaceutical with the highest concentrations, reaching 2 191 ng L⁻¹ in FUN. The non-target screening identified 125 chemicals, of which most were pharmaceuticals. The numbers of compounds identified and which were above the LOQ were higher in FUN and SIM, in agreement with results from the target analysis. Metformin is the compound with the highest risk to affect FUN reservoir negatively, based on calculated risk quotients. Considering that the reservoirs are used for multiple purposes, including water supply, irrigation, and aquaculture, it is important to continue investigating micropollutant occurrence to guarantee environmental and human health.