The anti-viral drug interferon-alpha (IFN-alpha) is widely-known to induce psychiatric and cognitive effects in patients. Previous work has shown that physical exercise can have a positive effect against brain insult. We investigated the effects of a clinically-comparable treatment regime of IFN-alpha on cognitive function in male Wistar rats and assessed the impact of chronic treadmill running on the deficits generated by IFN-alpha. We found that IFN-alpha induced significant impairments in performance on both spatial novelty and object novelty recognition. Chronic forced exercise did not protect against IFN-alpha-induced learning deficits in reactivity to spatial change, but did restore the capacity for novel object recognition in IFN-alpha-treated animals.