Coyotes are exposed to many parasites and pathogens of veterinary and zoonotic concern. To assess the prevalence of the diseases caused by these microbes, we opportunistically obtained coyote samples from a variety of sources including a GPS collaring study, rabies testing facilities, wildlife resources agents, and road-side mortalities. We performed necropsies, serological testing, fecal flotations, and molecular analyses on coyotes from Tennessee and South Carolina. Dirofilaria immitis (heartworm) infected 46% (41/89) of coyotes and was associated with eosinophilic alveolitis and arteritis. Paragonimus kellicotti, a zoonotic lung fluke, was found in 24% (17/71) of Tennessee coyotes, including one coyote with extrapulmonary infection affecting the liver and lymph nodes. Trichinella spp., a zoonotic nematode, was present in 17% (12/71) of Tennessee coyotes but was not associated with muscular inflammation. Sarcoptes scabiei, the causative agent of sarcoptic mange, was detected in one Tennessee coyote. Most coyotes (86% [90/105]) were seropositive for Toxoplasma gondii, while 8.5% (9/106) were seropositive for Trypanosoma cruzi, an emerging zoonotic, vector-borne parasite. This study demonstrated that coyotes are commonly exposed to numerous parasites and pathogens that affect people and pets and are excellent sentinels for these diseases.