Mental practice with motor imagery improves motor performance, for example reducing the duration of goal-directed movements. However, it is not known whether an experimental session involving prolonged sequences of motor imagery induces mental fatigue and alters motor and mental performances. In this study, participants imagined 100 point-to-point arm movements combined with actual pointing movements every 10 or 50 imagined movements. Participants reported a subjective feeling of mental fatigue after imagining 100 pointing movements. When participants performed actual movements every 50 imagined movements, the duration of both actual and imagined movements increased at the end of the protocol. On the contrary, no change in actual and imagined movement duration was observed when participants performed actual movements every 10 imagined movements. These results suggested that the repetition of many imagined movements induced mental fatigue and altered the mental simulation and the actual execution processes of the movement. However, the regular execution of actual movements seemed to counteract the negative effect of mental fatigue as both actual and imagined movement duration remained constant with actual trials inserted between mental rehearsals. We suggest that during training or rehabilitation programs, actual movements should be executed and/or imagined movement duration should be controlled to avoid the negative effects of mental fatigue on motor performance.