A review of archival cases at Northwest ZooPath from 1995–2018 identified 16/96 (17%; eight females, eight males) lesser kudus (Tragelaphus imberbis) with chronic pancreatic disease (CPD) from three institutions, all of which originated from an initial founder stock of 12 animals. Ages at time of death or euthanasia ranged from 2 to 132 mo (average age = 69 mo). All cases had varying degrees of pancreatic acinar cell depletion, ductular hyperplasia, and fibrosis. Serum fructosamine, glucose, insulin, and insulin to glucose ratio collected close to time of death from 13 affected animals were not significantly different from controls (n = 19). Of these analytes, receiver operating characteristic analysis identified fructosamine as the best-performing analyte with an area under the curve 0.671 (95% confidence interval = 0.480–0.828; sensitivity = 58.3%, specificity = 84.2%; cutoff point >352 µmol/L) in the diagnosis of CPD. With a 15% prevalence, there was a positive predictive value of 41% and a negative predictive value of 92%, indicating that the probability of false positives is high, but of false negatives is low. An etiologic agent was not identified by histology (n = 16), transmission electron microscopy (n = 1), or enterovirus PCR (n = 2). Serum zinc and hepatic heavy metal analyses were judged to be within normal limits. Chronic pancreatic disease is considered an important cause of morbidity and mortality in the lesser kudu; serum chemistry analysis warrants further investigation in its use for diagnosis. The etiopathogenesis is not understood, but the absence of obvious causes, the occurrence also in very young animals, and the inbred lineage of lesser kudus in the United States suggest a genetic basis for this disease.