A 19-yr-old, 78.2-kg captive female Indochinese tiger (Panthera tigris corbetti) from the El Paso Zoo (El Paso, Texas, USA) with chronic renal disease was euthanized after a 10-day course of anorexia, depression, progressive rear limb weakness, muscle fasciculations, and head tremors. Postmortem findings included pericardial effusion, generalized lymphadenopathy, glomerulosclerosis, glomerular atrophy with membranous glomerulonephropathy, and pancreatic adenocarcinoma. Pyogranulomatous pneumonia, pericarditis, and lymphadenitis were associated with fungal spherules histomorphologically consistent with Coccidioides immitis. Rising antibodies to C. immitis were detected on samples obtained perimortem and 2 mo before euthanasia. Retrospective serology was negative for two additional Indochinese tigers, two Iranian leopards (Panthera pardus saxicolor), two jaguars (Panthera onca), two bobcats (Lynx rufus texensis), two ocelots (Leopardus pardalis), and three Amur leopards (Panthera pardus orientalis) housed at the zoo over an 8-yr period. Despite being located within the endemic region for C. immitis, this is only the second case of coccidioidomycosis reported from this institution.