Hypoxia is one of the fundamental threats to water quality globally, particularly for partially enclosed basins with limited water renewal, such as coastal lagoons. This work proposes the combined use of a machine learning technique, field observations, and data derived from a hydrodynamic and heat exchange numerical model to predict, and forecast up to 10 days in advance, the occurrence of hypoxia in a eutrophic coastal lagoon. The random forest machine learning algorithm is used, training and validating a set of models to classify dissolved oxygen levels in the lagoon. The Orbetello lagoon, in the central Mediterranean Sea (Italy), has provided a test case for assessing the reliability of the proposed methodology. Results proved that the methodology is effective in providing a reliable short-term evaluation of DO levels, with a high resolution in both time and space throughout an entire lagoon. An overall classification accuracy of up to 91 % was found in the models, with a score for identifying the occurrence of severe hypoxia - i.e. hourly DO levels lower than 2 mg/l - of 86 %. The use of predictors extracted from a numerical hydrodynamic model allows us to overcome the intrinsic limitation of machine learning modelling approaches which rely on input data from relatively few, local field measurements, i.e. the inability to capture the spatial heterogeneity of DO distributions, unless several measuring points are available. The methodological approach is proposed for application to similar eutrophic environments.