This paper presents the design, development, and implementation of a bioinspired fault diagnosis scheme applied to a cold gas–based spacecraft prototype. The proposed framework relies on the artificial immune system metaphor with the goal of monitoring the health of the spacecraft by detecting subsystem upset conditions such as actuator malfunctions. A nonlinear dynamic inversion baseline controller with adaptation capabilities has been developed and implemented for attitude control of the spacecraft. The performance of the proposed health-monitoring scheme is determined by analyzing the system response under different actuator failures while the spacecraft is operated with and without adaptive augmentation. In both cases, the results show acceptable performance in terms of high detection activity and low false alarms with real-time capabilities. The application of this artificial intelligence–based scheme to aerospace systems will provide a high impact on space exploration by increasing mission protection and performance.