Although it has been shown that exposure to HZE particles disrupts cognitive performance when tested 2–4 weeks after irradiation, it has not been determined whether exposure to HZE particles acutely affects cognitive performance, i.e., within 4–48 h after exposure. The current experiments were designed to determine the acute effects of exposure to HZE particles (¹⁶O and ⁵⁶Fe) on cognitive performance and whether exposure to HZE particles affected learning or memory, as well as to understand the relationship between acute changes in the levels of NOX2 (a measure of oxidative stress) and COX2 (a measure of neuroinflammation) in specific brain regions and cognitive performance. The results of these studies indicate that the acute effects of radiation exposure on cognitive performance are on memory, not learning. Further, the acute effects of exposure to HZE particles on oxidative stress and neuroinflammation and their relationship to cognitive performance indicate that, although the effects of exposure to both ⁵⁶Fe and ¹⁶O are widespread, only changes in specific regions of the brain may be related to changes in cognitive function.