In 2015, an emergency state was declared in Bolivia when Poopó Lake dried up. Climate variability and the increasing need for water are potential factors responsible for this situation. Because field data are missing over the region, no statements are possible about the influence of mentioned factors. This study is a preliminary step toward the understanding of Poopó Lake drought using remote sensing data. First, atmospheric corrections for Landsat (FLAASH and L8SR), seven satellite derived indexes for extracting water bodies, MOD16 evapotranspiration, PERSIANN-CDR and MSWEP rainfall products potentiality were assessed. Then, the fluctuations of Poopó Lake extent over the last 26 years are presented for the first time jointly, with the mean regional annual rainfall. Three main droughts are highlighted between 1990 and 2015: two are associated with negative annual rainfall anomalies in 1994 and 1995 and one associated with positive annual rainfall anomaly in 2015. This suggests that other factors than rainfall influenced the recent disappearance of the lake. The regional evapotranspiration increased by 12.8% between 2000 and 2014. Evapotranspiration increase is not homogeneous over the watershed but limited over the main agriculture regions. Agriculture activity is one of the major factors contributing to the regional desertification and recent disappearance of Poopó Lake.