Two rare endemic carnivores occur on California's northern Channel Islands: island spotted skunks (Spilogale gracilis amphiala) and island foxes (Urocyon littoralis). As insular carnivores, both may be particularly vulnerable to novel pathogens. We tested sera from 31 island spotted skunks on Santa Cruz Island, where both skunks and foxes occur sympatrically, to establish their exposure to disease agents. One skunk (3%) tested positive for canine heartworm, and 3 skunks (10%) tested positive for canine parvovirus. None showed evidence of exposure to canine adenovirus, canine distemper virus, canine herpesvirus, Leptospira bacteria (serovars pomona, canicola, and icterohaemorrhagiae), or pseudorabies virus. Spotted skunks on Santa Cruz Island apparently have low susceptibility or exposure to these pathogens and are unlikely to be reservoirs of these diseases for island foxes.