A survey of wild rodents was performed in the Morro Bay area of central coastal California to determine serological and polymerase chain reaction (PCR) prevalence of Anaplasma phagocytophilum Dumler, Barbet, Bekker, Dasch, Palmer, Ray, Rikihisa, and Rurangirwa, Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt, and Brenner, Francisella tularensis McCoy, and Yersinia pestis Yersin; to describe the ectoparasitic fauna on important vector-borne disease hosts; and to determine whether pathogen exposure was associated with infestation by ectoparasites. We trapped 411 rodents from 10 species in 2004 and 2005. Anaplasma phagocytophilum exposure was detected in 11% of all wild rodents tested, with seropositive animals in eight species. Anaplasma phagocytophilum DNA was detected by PCR amplification in Neotoma fuscipes Baird and Reithrodontomys megalotis Baird (0.6% of all rodents). Yersinia spp. exposure was identified in 3.2% of all rodents tested, with highest detected exposure in peridomestic rodents, Mus musculus L. (20%), and Rattus rattus L. (50%). No individuals tested positive for the Y. pestis pla gene by PCR. In total, 338 fleas were identified from each of 10 rodent species examined. The most abundant flea was Malareus telchinus Rothschild. Relative density of flea infestation was highest on Spermophilus beecheyi Richardson and Microtus californicus Peale. Ticks recovered from trapped animals included Ixodes angustus Neumann, Ixodes pacificus Cooley & Kohls, Ixodes spinipalpis Hadwen & Nuttall, and Dermacentor occidentalis Marx. Given the moderate climate and diversity of rodents and arthropods in the Morro Bay area, ongoing investigation of this region will be helpful in understanding disease maintenance cycles.