Five neonatal Pallas' cats (Otocolobus manul) at the Oklahoma City Zoo died from toxoplasmosis with concurrent herpesvirus infection. These multiple infections suggested underlying immunodeficiency, perhaps caused by concurrent infection with feline immunodeficiency virus (FIV); so blood samples were collected for serology, serum protein electrophoresis, lymphocyte proliferation assays, and cytokine analysis by reverse transcriptase–quantitative competitive polymerase chain reaction (RT-qcPCR). Resulting data were compared with data from FIV-infected and control domestic short-haired cats. In addition, peripheral blood mononuclear cell cultures were propagated to detect FIV virus by both RT-qcPCR and detection of reverse transcriptase activity. Serum protein electrophoresis showed that four of six Pallas' cats had increased alpha₂ globulins. At least two Pallas' cats had decreased lymphoproliferation responses to mitogen, and all three tested animals exhibited defective interleukin-12 gene expression. Although these clinical and laboratory findings suggested an immunodeficiency syndrome, FIV infection could not be confirmed. On the basis of repeated blood test results, it can be concluded that nutritional, metabolic, or other systemic problems probably did not contribute to the disease syndrome. Further investigation of other possible causes of immunodeficiency, including a possible genetic component, in this population is needed.