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Animal hoarders accumulate animals in over-crowded conditions without adequate nutrition, sanitation, and veterinary care. As a result, animals rescued from hoarding frequently have a variety of medical conditions including respiratory infections, gastrointestinal disease, parasitism, malnutrition, and other evidence of neglect. The purpose of this study was to characterize the infectious diseases carried by clinically affected cats and to determine the prevalence of retroviral infections among cats in large-scale cat hoarding investigations. Records were reviewed retrospectively from four large-scale seizures of cats from failed sanctuaries from November 2009 through March 2012. The number of cats seized in each case ranged from 387 to 697. Cats were screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) in all four cases and for dermatophytosis in one case. A subset of cats exhibiting signs of upper respiratory disease or diarrhea had been tested for infections by PCR and fecal flotation for treatment planning. Mycoplasma felis (78%), calicivirus (78%), and Streptococcus equi subspecies zooepidemicus (55%) were the most common respiratory infections. Feline enteric coronavirus (88%), Giardia (56%), Clostridium perfringens (49%), and Tritrichomonas foetus (39%) were most common in cats with diarrhea. The seroprevalence of FeLV and FIV were 8% and 8%, respectively. In the one case in which cats with lesions suspicious for dermatophytosis were cultured for Microsporum canis, 69/76 lesional cats were culture-positive; of these, half were believed to be truly infected and half were believed to be fomite carriers. Cats from large-scale hoarding cases had high risk for enteric and respiratory infections, retroviruses, and dermatophytosis. Case responders should be prepared for mass treatment of infectious diseases and should implement protocols to prevent transmission of feline or zoonotic infections during the emergency response and when transferring the rescued cats to other shelters or to adopters.