Worldwide, pristine environments are influenced by human societies. In the Galapagos Islands, the endangered, endemic Galapagos sea lion (Zalophus wollebaeki) has formed one of the biggest colonies within the town center of Puerto Baquerizo Moreno. About 8,000 people live there and human wildlife interactions occur daily. With colony counts and direct observations from 2008 to 2012, we analyze cause of death, injuries and disease of urban sea lion colonies at Wreck Bay. Population increase since 2008 can be attributed to an immigration of adult sea lions in 2010, resulting in an increase in the pup and juvenile production in 2011 and 2012. Pup mortality increased drastically to 2009 and again in 2011 and 2012. Besides pup mortality, most of the deaths are caused by increased disease incidences and human activity. Our observations suggest that overall 65% of the injuries observed are produced by human interaction. The increase in threats leading to death, injuries or disease can have long-term effects on the population. Although threats that cause physical injuries can be managed locally, sea lions range movements contributes to the spread of infectious pathogens, which may affect neighbor colonies and potentially have an impact on the survival of the species. Our study reveals the need of stronger efforts towards a more complete understanding of threats and especially disease spread among Galapagos Sea lions in urban environments and the establishment of more effective management measures.