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Introduction: The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. Methods: This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. Results: A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74–18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60–3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58–3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. Conclusion: Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status. [ABSTRACT FROM AUTHOR]