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Large carnivores have been largely extirpated from Southeast Asia due to deforestation, habitat fragmentation, and poaching. Estimating the density of endangered carnivore populations, and identifying relationships between species occupancy and both environmental and anthropogenic factors, is essential for effective conservation planning. Recently, the IUCN conservation status of the Indochinese leopard (Panthera pardus delacouri) was upgraded to “Critically Endangered.” We surveyed Kweekoh Wildlife Sanctuary in Kawthoolei, an area administered by the Karen ethnic group in eastern Myanmar, to quantify (1) leopard population density using spatially explicit mark‐resight (SMR) models, (2) leopard occupancy as influenced by important ecological variables, and (3) potential differences in activity between melanistic and spotted leopard morphs. Leopard density was estimated to be 1.39 ± SE 0.22/100 km2. Leopard occupancy (ψ = 0.43; 95% credible interval: 0.26–0.67) increased further from roads, at relatively higher elevations, and in areas with higher relative abundance of wild boar. Leopard activity was cathemeral, with higher activity during night hours, and significant overlap (Δ = 0.84; 95% confidence interval: 0.71–0.96) between melanistic and spotted morphs. However, melanistic leopards were more active during twilight hours than spotted individuals whose activity did not significantly vary throughout the day. Indochinese leopard density estimates in Kweekoh were among the lowest reported from Southeast Asia. Leopard occupancy was highest in the sanctuary's core areas, suggesting the presence of negative anthropogenic impacts along the sanctuary borders. We suggest our low density estimates warrant immediate and decisive conservation action, including better protection for leopards, their habitat, and their prey.