Abstract Background A degenerative left shift (DLS) is reported to be a poor prognostic indicator in dogs and cats. Limited data in dogs and no studies in cats have been published to investigate this claim. Hypothesis/Objectives To characterize the feline population affected by DLS and to determine if the presence and severity of DLS are associated with increased risk of euthanasia or death. Animals One hundred and eight cats with DLS (cases) and 322 cats without DLS (controls) presented to the University of California, Davis Veterinary Medical Teaching Hospital between April 1, 1995 and April 1, 2010. Methods Retrospective case–control study. All cases had a CBC performed within 24 hours of presentation in which immature granulocytic precursors exceeded mature neutrophils. Controls were matched by year of presentation and primary diagnosis. Survival analysis was used to determine risk of death or euthanasia from DLS and other potential predictors of outcome. Results Cases were more likely to die or be euthanized in hospital compared to controls (60/108 [56%] versus 107/322 [33%]). DLS was a significant predictor of death or euthanasia in hospitalized cats in both univariate and multivariate analysis (hazard ratio, 1.57; 95% confidence interval, 1.13–2.18). Trend analysis showed an increasing trend in the hazard of euthanasia or death with increasing severity of DLS. Conclusions and Clinical Importance Cats with DLS are 1.57 times more likely to die or be euthanized in hospital than cats without DLS. In addition, increasing severity of DLS is associated with increased likelihood of death or euthanasia.