ObjectiveTo evaluate clinicopathological variables associated with hospital mortality in critically ill cats with compromised hemodynamics and tissue hypoperfusion.DesignRetrospective observational study.SettingPrivate referral center.AnimalsFifty‐seven critically ill cats with compromised hemodynamics or tissue hypoperfusion.InterventionsNone.Measurements and Main ResultsThe electronic medical records were searched for all cats admitted from June 2014 to November 2020. Cats were included in the study if the medical records clearly identified the presence of compromised hemodynamics and tissue hypoperfusion. Blood samples were obtained by percutaneous puncture of the external jugular vein, and blood gases, electrolytes, L‐lactate concentration, and glucose were measured by a point‐of‐care analyzer. A predictive logistic regression model for mortality was performed. A total of 57 cats were ultimately included in the study. Thirty‐five cats died. Eighteen of them were euthanized because of the severity of illness, and 17 died naturally. Twenty‐two cats were discharged alive from the hospital. After adjusting for the Acute Patient Physiologic and Laboratory Evaluation (APPLE) fast score and disease category, jugular venous partial pressure of oxygen (Pvjo2) and HCT at admission were independent predictors of hospital mortality (HCT: odds ratio [OR], 0.763, 95% confidence interval [CI]: 0.625–0.930; P = 0.008; Pjvo2: OR, 0.858; 95% CI: 0.749–0.984; P = 0.029). The association of these variables with mortality was maintained after conducting a sensitivity analysis and excluding cats that died by euthanasia.ConclusionsIn cats with hemodynamic instability and tissue hypoperfusion, HCT and Pvjo2 behaved as independent predictors of mortality. Both variables seem to reflect the magnitude of oxygen debt and tissue hypoperfusion.