Background Cats in respiratory distress have limited tolerance for manipulation, hindering clinical monitoring. Minute volume (MV) can be utilized to rate dyspnea in humans, but its relationship with respiratory distress in cats remains poorly investigated. Hypothesis Cats with respiratory distress will show higher MV per kg body weight (MV/BW) than normal cats, and the MV/BW increase will correlate with survival. Animals Fifty‐two cats with respiratory distress from lung parenchymal disease, pleural space disease, lower airway obstruction (LAO), or upper airway obstruction were recruited since 2014. Methods This is a prospective observational study. Study cats were placed in a transparent chamber, allowing clinicians to easily observe their breathing status and record ventilation using barometric whole‐body plethysmography (BWBP). Ventilatory variables of the 52 cats were compared with those of 14 historic control cats. Follow‐up data, including disease category, clinical outcomes, and survival, were prospectively collected. Results Cats in respiratory distress demonstrated significantly higher MV/BW (397 mL/kg; range, 158‐1240) than normal cats (269 mL/kg; range, 168‐389; P < .001). Among the etiologies, cats with LAO, parenchymal, and pleural space disease exhibited higher‐than‐normal MV/BW trends. A cutoff value of 373 mL/kg (1.4‐fold increase) indicated abnormally increased breathing efforts (sensitivity, 67%; specificity, 93%). MV/BW was independently associated with increased cardiorespiratory mortality in cats with respiratory distress (adjusted hazard ratio 1.17, 95% confidence interval CI 1.02‐1.35; P = .03). Conclusions and Clinical Importance Breathing efforts in cats can be noninvasively quantified using BWBP. Measurement of MV/BW could serve as a prognostic index for monitoring cats experiencing respiratory distress.