Six feline cases of Influenza A (HPAI H5N1) have been diagnosed in domestic cats in Colorado during 2024. One of these cases was directly associated with a known infected commercial dairy facility. Two of the six cases were indoor only cats with no direct exposures to the virus. Three of the six cases were known indoor/outdoor cats that hunted mice and/or small birds as prey and also spent time indoors with their owners. Five of the six cases have presented with similar clinical signs and disease progression: an initial complaint of lethargy and inappetence, followed by progressive respiratory signs in some and fairly consistent progressive neurologic signs in most. Several of these cases were tested for rabies preceding diagnosis with H5N1 infection due to the indistinguishable presentation once neurologic signs presented. HPAI H5N1 infection should be considered in domestic felines even if all of the risk factors or clinical signs are not present. There is high abundance of virus in Colorado at this time, predominantly being detected in domestic dairy cattle in commercial dairy herds with spillover into mammals and wild birds on and near these premises. Notably the B3.13 strain of the Eurasian 2.3.4.4b clade H5N1 virus has been spreading in animals not historically attributed as reservoirs for the HPAI virus. This lineage of virus has not been detected in migratory waterfowl at this time.