NASA's decision to resume manned deep space mission, first to the Moon and then Mars, necessitated a detailed assessment of the potential health effects that astronauts may experience on long-duration missions. Multiple studies suggest that there may be significant space radiation (SR)-induced impairment of neurocognitive processes, including advanced executive functions. However, given the multitude of SR-induced changes in the CNS, it is possible that completely different SR-induced sequelae will be induced in previously exposed individuals. Thus, current risk estimates are likely to be pertinent only for the early stages of a deep space mission, and even then only for astronauts that have no previous experience in space.In this study, rats that maintained high attentional set shifting (ATSET) performance after an initial exposure to 10 cGy of SR (either 250 MeV/n He or GCRsim), were exposed to an additional dose of 10 cGy GCRsim and their ATSET performance reassessed. The re-irradiated rats exhibited significant impairment of ATSET performance, however, the performance decrements differed in two important aspects from those typically observed after single exposures. First, the decrements were manifested when the rats were required to perform set shifting, specifically in the IDR and EDS stages of the ATSET test. Secondly, the main performance decrement was in a loss of processing speed, which in the IDR stage resulted in the re-irradiated rats taking 2-fold more time to solve the problem than did Sham rats. The functional consequence of this decrement was that compared to Sham rats, 20 % fewer SR-exposed rats solved the IDS and EDR problems within 20 s.These data suggests that prior SR exposure alters nature of ATSET impairments from that observed in radiation-naïve individuals. Risk estimates derived from studies that use radiation naïve rats may thus not fully reflect the incidence and nature of ATSET performance deficits that could occur over the entire duration of a mission to Mars, or in astronauts who return to deep space on multiple occasions. It would thus be germane to conduct in-flight monitoring for cognitive performance decrements observed in both radiation naïve and exposed rats during the mission, and ensure that the crew has sufficient overlapping skill sets to minimize the operational impact of these additional cognitive impairments.