Cetaceans are considered environmental sentinels and their health often reflects either anthropogenic or natural spatio-temporal disturbances. This study investigated the pathological findings and mortality of small cetaceans with the aim of detecting hazards and monitoring health trends in a high-biodiversity area. Between 2007 and 2012, 218 stranded cetaceans were recorded on the Paraná coast, southern Brazil. Fifty-seven (26.1%) of these animals, including 50 Sotalia guianensis, 2 Pontoporia blainvillei, 2 Stenella frontalis, 1 Stenella longirostris, 1 Tursiops truncatus and 1 Globicephala melas were necropsied and samples were collected for histopathology. Causes of death were determined in 46 of the 57 (80.7%) animals and most (30 or 65.2%) were ascribed to anthropogenic activities, including fisheries bycatch (28/30) and trauma (2/30). The remaining 16 fatalities were considered natural, and attributed to pneumonia (10/16), emaciation (3/16), septicemia (1/16), neonatal pathology (1/16) and choking via food obstruction (1/16). Irrespective of the cause, bronchointerstitial pneumonia, associated with parasitism, lymphadenitis and membranous glomerulonephritis were common findings among all fatalities. These results suggest, that while anthropogenic activities are a leading cause of cetacean strandings in Paraná, underlying pre-existing diseases may contribute towards deaths. Although the studied area is considered a biosphere reserve by UNESCO, complex anthropogenic and natural interactions might be occurring, increasing cetacean susceptibility to hazards. This study may help facilitate developing an effective conservation plan for coastal cetaceans focusing on reducing fisheries interactions, habitat degradation and pollution as mechanisms for ultimately increasing species resilience.