Due to the relatively low offspring survival rate, surviving adult leopards play a critical role in the species’ viability. The unnatural mortality of leopards, caused by human activities can seriously compromise the species’ long-term population survival. An analysis of spatial distribution and sex ratio of unnatural mortality of 147 recorded Persian leopard (Panthera pardus saxicolor) carcasses during a fifteen-year period (from 2000–2015) in Iran indicated that road mortality is the second most frequent cause of unnatural mortality of Persian leopards’ after illegal hunting (or prey poisoning, such as poisoned meat) by villagers, shepherds and military forces. The greatest percent of unnatural mortality events were recorded in the Golestan provinc in the north of Iran and eastern most parts of the Hyrcanian forests. Using distribution models of species, based on road accident locations as species data, we mapped the species’ distribution and critical areas of unnatural mortality of Persian leopard that can be used in prioritizing leopard-human conflicts management. Our results showed that mortality records were significantly higher in non-protected compared to protected areas. Males constituted 65 percent of the records used in the study as males dispersed more widely compared to the females. This imbalance can have severe demographic effects. A large proportion of leopards’ activity, occurrence area, and habitat lies in non-protected areas, which is mirrored by the greater number of unnatural mortality outside protected areas. Most of the incidents were due to human factors, thus management interventions such as traffic speed limitations, signs, cameras, and faunal bridges as well as increasing public participation and awareness (especially among rural communities) will positively affect the species’ conservation programs. This research aimed to produce unnatural mortality of leopards’ risk map throughout Iran and discuss the different aspects of this phenomenon