In the Shuklaphanta National Park (Nepal), we sampled the spatial distributions and diel activity patterns of tigers and leopards during three winter (dry) seasons. Densities of both predators were similar and rather low (≤ 3/100 km²), but total prey base was high (> 150 animals/km²). From camera trapping, 20 different tigers and leopards were identified. While leopards (9) were confined to areas along the reserve border, tigers (11) were located significantly farther inside, where the abundance of large-sized wild prey was higher and that of small-sized prey lower than closer to the border. In the inter-specific spatial overlap zones, the two species were never photographed at the same locations. Diel activity patterns did not differ. Normally, leopards avoid tigers owing to social interference. In our study, the spatial segregation was interpreted to be due to low predator-prey ratios (e.g., food not limiting for either species), with each species distributed in areas with highest densities of their preferred prey. Social interference behavior – although probably occurring – played a minor role. The concentration of leopards along the reserve border, coupled with a diet that included domestic dogs, suggest that different behavioral adaptations to anthropogenic factors might also have played a role.