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ABSTRACT: Cytauxzoon felis is a tick-transmitted protozoan parasite of domestic and wild felids in the south-central and southeastern United States. Infection of domestic cats (Felis domesticus) with C. felis is typically acute and characterized by fever, anorexia, listlessness, anemia, icterus and usually death within 19-21 days. To determine the temporal occurrence and environmental risk factors associated with infection of C. felis in domestic cats from Oklahoma, information in the electronic medical records from the Oklahoma Animal Disease Diagnostic Laboratory (OADDL) and Boren Veterinary Medical Teaching Hospital (BVMTH) was retrospectively searched. A total of 232 cytauxzoonosis cases from 1995 to 2006 from OADDL (n=180) and 1998 to 2006 from BVMTH (n=52) were combined and analyzed. The number of cytauxzoonosis cases remained relatively consistent from year to year. Diagnosis of C. felis infection in domestic cats followed a bimodal pattern with a peak in the number of cases in April, May, and June followed by a second smaller peak in August and September. The majority (n=72; 31.0%) of cytauxzoonosis cases were diagnosed in May. No cases of C. felis infection were diagnosed in December and only a few (n=10; 4.3%) cases were observed from November through March during the 12-year period. In cases for which the client's address was available, geographic coordinates were assigned and landscape characteristics were quantified within a 100-m radius of each cytauxzoonosis case location. Of cytauxzoonosis cases (n=41) with a known client address, a majority (n=28; 68.3%) occurred in low density residential areas and more cases (n=8; 19.5%) were found in urban edge habitat than expected at random. Locations of diagnosed cytauxzoonosis cases were significantly associated with more wooded (31.8+/-4.03%) cover and closer (55.5+/-18.45m) proximity to natural or unmanaged areas than randomly selected control sites. Practicing and diagnostic veterinarians can expect to see a distinct temporal pattern in cases of cytauxzoonosis and more cases can be expected in domestic cats living in close proximity to environments that support tick vectors and bobcats.