Rett syndrome (RTT) is the second leading cause of mental disability in women and causes a serious neurodevelopmental disorder that leads to a global disability of the individual. Cognitive training has been shown to improve neuropsychological and neurophysiological parameters in similar pathologies. However, knowledge about neurophysiological training in RTT is scarce. The objective of the study was to evaluate the result and duration of the effect of cognitive stimulation over four consecutive days of training, in order to determine the viability of a long-term effect. Nineteen patients performed a cognitive task using an eye tracking device during the first three days of training. Prior to each training, a resting state EEG with eyes open was recorded to assess changes in spectral variables in the brain. An EEG recording at rest with eyes open was also acquired on the fourth day, in order to evaluate the differences with respect to the first day. Results showed a spectral shift to higher frequencies in a long-term period of four days. Significant positive alterations of brain rhythms were observed: decrease in low-frequency (delta) oscillations and an increase in high-frequency (beta) rhythms, resulting in more complex signals closer to non-pathological brain behavior. In conclusion, this study showed the potential long-term benefits of cognitive stimulation in RTT patients.