Human recreation has immediate and long-term impacts on wildlife, and exposure to recreational activities might be particularly high in urban systems. We investigated the relationship between human recreation and the spatial and temporal activity patterns of large mammals in an urban nature reserve. Data from remotely triggered infra-red cameras (1999–2001) were used to assess activity for bobcat, coyote, mule deer, humans, and domestic dogs along paths in the Nature Reserve of Orange County (NROC), California. Forty-nine camera sites established across the NROC yielded 16,722 images of humans, dogs, and our three target large mammal species during 4232 observation nights. Results suggest that bobcats, and to a lesser degree coyotes, exhibited both spatial and temporal displacement in response to human recreation. Bobcats were not only detected less frequently along trails with higher human activity, but also appeared to shift their daily activity patterns to become more nocturnal in high human use areas; negative associations between bobcat and human activity were particularly evident for bikers, hikers, and domestic dogs. In general, both bobcats and coyotes displayed a relatively wide range of activity levels at sites with low human use, but a lower and markedly restricted range of activity at those sites with the highest levels of recreation. Although we did not find a clear and consistent pattern of avoidance of human recreation by deer, the probability of detecting deer during the day was lower with increasing levels of human recreation. Future studies that experimentally investigate the impacts of recreationists on wildlife, as well as relate behavioral responses to survival and reproduction, will allow further insight of the effects of urban recreation on large mammal populations.