Hemolysis occurs frequently in patients requiring mechanical circulatory support (MCS) and is associated with worse outcomes. Carboxyhemoglobin (CO-Hb) has been suggested as a potential biomarker for detection of hemolysis and may be useful to guide clinicians’ decisions to anticipate worsening hemolysis and prevent hemolysis-related adverse events.

We performed a systematic review and meta-analysis of studies in PubMed, Embase, and Cochrane library with last search on September 2025 investigating the correlation between CO-Hb and hemolysis in patients requiring MCS. We included adult and pediatric patients undergoing support with MCS. Primary outcome was relationship between CO-Hb levels and hemolysis. Risk of bias was evaluated with Newcastle–Ottawa Scale tool. Hemolysis was collected through validated biomarkers or approved scores.

A total of 22 studies with 6566 patients were included. Eighteen studies investigated patients on ECMO, most of them on venovenous ECMO, and four studies on cardiopulmonary bypass. Four studies were eligible for quantitative synthesis and showed a positive correlation between pfHb and CO-Hb (fixed-effect model: r = 0.117, 95% confidence interval 0.086–0.147; I² = 21.7%; p < 0.0001). No studies reported data on timing of relative changes of CO-Hb and other hemolysis markers, detection of clinically relevant hemolysis, or start of ECLS.

CO-Hb is weakly but significantly correlated with pfHb. There is lack of data on clinically relevant CO-Hb cutoffs or changes related to other hemolysis markers or clinical detection of hemolysis.