Wildlife diseases have implications for ecology, conservation, human health, and health of domestic animals. They may impact wildlife health and population dynamics. Exposure rates of coyotes (Canis latrans) to pathogens such as Yersinia pestis, the cause of plague, may reflect prevalence rates in both rodent prey and human populations. We captured coyotes in north-central New Mexico during 2005–2008 and collected blood samples for serologic surveys. We tested for antibodies against canine distemper virus (CDV, Canine morbillivirus), canine parvovirus (CPV, Carnivore protoparvovirus), plague, tularemia (Francisella tularensis), and for canine heartworm (Dirofilaria immitis) antigen. Serum biochemistry variables that fell outside reference ranges were probably related to capture stress. We detected antibodies to parvovirus in 32/32 samples (100%), and to Y. pestis in 26/31 (84%). More than half 19/32 (59%) had antibodies against CDV, and 5/31 (39%) had antibodies against F. tularensis. We did not detect any heartworm antigens (n = 9). Pathogen prevalence was similar between sexes and among the three coyote packs in the study area. Parvovirus exposure appeared to happen early in life, and prevalence of antibodies against CDV increased with increasing age class. Exposure to Y. pestis and F. tularensis occurred across all age classes. The high coyote seroprevalence rates observed for CPV, Y. pestis, and CDV may indicate high prevalence in sympatric vertebrate populations, with implications for regional wildlife conservation as well as risk to humans via zoonotic transmission.