Serological and genetic material collected over 15 years (1990–2004) from 207 cougars (Puma concolor) in four populations in the Rocky Mountains were examined for evidence of current or prior exposure to feline immunodeficiency virus (FIV), feline parvovirus (FPV), feline coronavirus (FCoV), feline calicivirus (FCV), canine distemper virus (CDV), feline herpesvirus (FHV), and Yersinia pestis. Serologic data were analyzed for annual variation in seroconversions to assess whether these pathogens are epidemic or endemic in cougars, and to determine whether family membership, age, sex, or location influence risk of exposure. FIV and FPV were clearly endemic in the studied populations, whereas exposure to FCoV, FCV, CDV, and Y. pestis was more sporadic. No evidence was found for FHV. Age was the most consistent predictor of increased exposure risk, often with no other important factors emerging. Evidence for transmission within family groups was limited to FIV and FCoV, whereas some indication for host sex affecting exposure probability was found for FIV and Y. pestis. Overall, cougar populations exhibited few differences in terms of pathogen presence and prevalence, suggesting the presence of similar risk factors throughout the study region.