Acute respiratory distress syndrome (ARDS) carries high mortality, and conventional physiological indices incompletely reflect disease trajectory and outcomes. Endogenous carboxyhemoglobin (COHgb), a marker of heme oxygenase–1 activity and oxidative stress, may offer additional prognostic value. This study evaluated whether arterial COHgb levels, measured at defined stages of ARDS, are associated with mortality, intensive care unit (ICU) free days, and ventilator-free days, and whether these associations differ between COVID-19 and non–COVID-19 ARDS.

In this retrospective cohort study (2017–2021), non-smoking adults meeting Berlin criteria for ARDS across two ICUs were included. COHgb and physiological parameters were recorded at the predefined time periods of ARDS. The primary outcome was in-hospital mortality; secondary outcomes included ICU-free and ventilator-free days. Multivariable logistic regression and receiver operating characteristic analyses compared the predictive performance of COHgb with APACHE II, SOFA, SAPS II scores, and PaO ₂ /FiO ₂ ratio.

Ninety-five patients were analyzed (42 survivors, 53 non-survivors). Day 3 COHgb was higher in non-survivors than survivors (median 1.47 vs. 0.97; P = 0.002). In multivariable analysis, only Day 3 COHgb independently predicted mortality (adjusted OR 3.15; 95% CI 1.19–8.32; P = 0.020) with an AUC of 0.70 (sensitivity 69%, specificity 64%). Findings were consistent across COVID-19 and non–COVID-19 subgroups.

Arterial COHgb may serve as a prognostic marker of mortality in ARDS, after adjustment for established severity scores and oxygenation indices. Given the modest sample size, these results should be viewed as hypothesis generating and require confirmation in larger, multicenter cohorts.