Investigations into the cause of mortality and other important findings at necropsy were made into two families of small mammals at the Smithsonian National Zoological Park (SNZP; USA). Necropsy reports from 1976 through 2008 were reviewed for all elephant shrews in family Macroscelididae (n = 118) and all tree shrews in family Tupaiidae (n = 90) that lived for greater than 30 days at the SNZP. Causes of mortality were classified by body system and etiology to identify prevalent diseases and trends across demographics for each family. In elephant shrews, gastrointestinal disease (n = 18) and respiratory disease (n = 22) were important causes of mortality with an increased prevalence of pneumonia in adult males. Trauma was a common cause of mortality in tree shrews (n = 22). Cryptococcosis was an important cause of mortality in both families (n = 8 elephant shrews; n = 13 tree shrews). Bacterial infections, often systemic at time of mortality, were also common (n = 16 elephant shrews; n = 17 tree shrews). Arteriosclerosis was a common comorbid pathology noted at necropsy in certain populations, seen only in Elephantulus rufescens in the family Macroscelididae (n = 22) and in only males in the family Tupaiidae (n = 11). Gongylonemiasis was seen commonly in tree shrews (n = 15), as a comorbid finding, or in 5 cases directly leading to mortality. Awareness of the prevalence of these diseases can help guide prevention and intervention strategies.