Most modern Earth and Universe observation spacecraft are now equipped with large lightweight and flexible structures, such as antennas, telescopes, and extendable elements. The trend of hosting more complex and bigger appendages, essential for high-precision scientific applications, made orbiting satellites more susceptible to performance loss or degradation due to structural damages. In this scenario, Structural Health Monitoring strategies can be used to evaluate the health status of satellite substructures. However, in particular when analysing large appendages, traditional approaches may not be sufficient to identify local damages, as they will generally induce less observable changes in the system dynamics yet cause a relevant loss of payload data and information. This paper proposes a deep neural network to detect failures and investigate sensor sensitivity to damage classification for an orbiting satellite hosting a distributed network of accelerometers on a large mesh reflector antenna. The sensors-acquired time series are generated by using a fully coupled 3D simulator of the in-orbit attitude behaviour of a flexible satellite, whose appendages are modelled by using finite element techniques. The machine learning architecture is then trained and tested by using the sensors’ responses gathered in a composite scenario, including not only the complete failure of a structural element (structural break) but also an intermediate level of structural damage. The proposed deep learning framework and sensors configuration proved to accurately detect failures in the most critical area or the structure while opening new investigation possibilities regarding geometrical properties and sensor distribution.