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Remote sensing imagery are fundamental to increasing the knowledge about sediment dynamics in the middle-lower Amazon floodplains. Moreover, they can help to understand both how climate change and how land use and land cover changes impact the sediment exchange between the Amazon River and floodplain lakes in this important and complex ecosystem. This study investigates the suitability of Landsat-8 and Sentinel-2 spectral characteristics in retrieving total (TSS) and inorganic (TSI) suspended sediments on a set of Amazon floodplain lakes in the middle-lower Amazon basin using in situ Remote Sensing Reflectance (R-rs) measurements to simulate Landsat 8/OLI (Operational Land Imager) and Sentinel 2/MSI (Multispectral Instrument) bands and to calibrate/validate several TSS and TSI empirical algorithms. The calibration was based on the Monte Carlo Simulation carried out for the following datasets: (1) All-Dataset, consisting of all the data acquired during four field campaigns at five lakes spread over the lower Amazon floodplain (n = 94); (2) Campaign-Dataset including samples acquired in a specific hydrograph phase (season) in all lakes. As sample size varied from one season to the other, n varied from 18 to 31; (3) Lake-Dataset including samples acquired in all seasons at a given lake with n also varying from 17 to 67 for each lake. The calibrated models were, then, applied to OLI and MSI scenes acquired in August 2017. The performance of three atmospheric correction algorithms was also assessed for both OLI (6S, ACOLITE, and L8SR) and MSI (6S, ACOLITE, and Sen2Cor) images. The impact of glint correction on atmosphere-corrected image performance was assessed against in situ glint-corrected R-rs measurements. After glint correction, the L8SR and 6S atmospheric correction performed better with the OLI and MSI sensors, respectively (Mean Absolute Percentage Error (MAPE) = 16.68% and 14.38%) considering the entire set of bands. However, for a given single band, different methods have different performances. The validated TSI and TSS satellite estimates showed that both in situ TSI and TSS algorithms provided reliable estimates, having the best results for the green OLI band (561 nm) and MSI red-edge band (705 nm) (MAPE < 21%). Moreover, the findings indicate that the OLI and MSI models provided similar errors, which support the use of both sensors as a virtual constellation for the TSS and TSI estimate over an Amazon floodplain. These results demonstrate the applicability of the calibration/validation techniques developed for the empirical modeling of suspended sediments in lower Amazon floodplain lakes using medium-resolution sensors.