Large charismatic predators have been re-introduced to several fenced reserves (<1000 km²); consequently, their populations can be at risk to declining genetic diversity and catastrophic events such as disease. Welgevonden Game Reserve (WGR) experienced an outbreak of canine distemper virus (CDV) in its lion (Panthera leo) population between October 2015 and February 2016. The decline was attributed to both direct CDV mortalities and indirect management interventions with a population decrease of 93%. In addition, the first documented cases of CDV were recorded in a brown hyaena (Hyaena brunnea) population. This article shares the management of a disease outbreak in WGR's lion population. It discusses the population history, the making of clinical observations leading to diagnoses and recommends strategies that can be implemented to prevent extirpation. The sourcing of new lions from established meta-populations, and the use of vaccinations to proactively prevent future outbreaks in managed wild lions is discussed. In less than two years the population has recovered. This paper provides a case report for wildlife practitioners of small populations of managed wild lions.