While the impacts of climate change on individual species and communities have been well documented there is little evidence on climate-mediated changes for entire ecosystems. Pristine alpine environments can provide unique insights into natural, physical and ecological response to climate change yet broad scale and long-term studies on these potential ‘ecosystem sentinels’ are scarce. We addressed this issue by examining cover changes of 1689 high-elevation wetlands (temporarily or perennial water-saturated grounds) in the Bolivian Cordillera Real, a region that has experienced significant warming and glacier melting over the last 30 years. We combined high spatial resolution satellite images from PLEIADES with the long-term images archive from LANDSAT to 1) examine environmental factors (e.g., glacier cover, wetland and watershed size) that affected wetland cover changes, and 2) identify wetlands’ features that affect their vulnerability (using habitat drying as a proxy) in the face of climate change. Over the (1984–2011) period, our data showed an increasing trend in the mean wetland total area and number, mainly related to the appearance of wet grassland patches during the wetter years. Wetland cover also showed high inter-annual variability and their area for a given year was positively correlated to precipitation intensities in the three months prior to the image date. Also, round wetlands located in highly glacierized catchments were less prone to drying, while relatively small wetlands with irregularly shaped contours suffered the highest rates of drying over the last three decades. High Andean wetlands can therefore be considered as ecosystem sentinels for climate change, as they seem sensitive to glacier melting. Beyond the specific focus of this study, our work illustrates how satellite-based monitoring of ecosystem sentinels can help filling the lack of information on the ecological consequences of current and changing climate conditions, a common and crucial issue especially in less-developed countries.