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Understanding and monitoring the ecological quality of coastal waters is crucial for preserving marine ecosystems. Eutrophication is one of the major problems affecting the ecological state of coastal marine waters. For this reason, the control of the trophic conditions of aquatic ecosystems is needed for the evaluation of their ecological quality. This study leverages space-based Sentinel-3 Ocean and Land Color Instrument imagery (OLCI) to assess the ecological quality of Mediterranean coastal waters using the Trophic Index (TRIX) key indicator. In particular, we explore the feasibility of coupling remote sensing and machine learning techniques to estimate the TRIX levels in the Ligurian, Tyrrhenian, and Ionian coastal regions of Italy. Our research reveals distinct geographical patterns in TRIX values across the study area, with some regions exhibiting eutrophic conditions near estuaries and others showing oligotrophic characteristics. We employ the Random Forest Regression algorithm, optimizing calibration parameters to predict TRIX levels. Feature importance analysis highlights the significance of latitude, longitude, and specific spectral bands in TRIX prediction. A final statistical assessment validates our model’s performance, demonstrating a moderate level of error (MAE of 0.51) and explanatory power (R2 of 0.37). These results highlight the potential of Sentinel-3 OLCI imagery in assessing ecological quality, contributing to our understanding of coastal water ecology. They also underscore the importance of merging remote sensing and machine learning in environmental monitoring and management. Future research should refine methodologies and expand datasets to enhance TRIX monitoring capabilities from space.