BACKGROUND: Respiratory sarcopenia is associated with poor outcomes, yet effective biomarkers for risk stratification remain limited. This study investigates the associations between complete blood count (CBC)-derived inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), neutrophil-monocyte-to-lymphocyte ratio (NMLR), and systemic inflammation response index (SIRI) and both all-cause and cardiovascular mortality in patients with respiratory sarcopenia. METHODS: We conducted a cohort analysis of 1,673 adults with possible respiratory sarcopenia using data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012, with mortality follow-up through December 31, 2019. Possible respiratory sarcopenia was assessed via peak expiratory flow rate (PEFR). Multivariable Cox regression models evaluated associations between NLR, NMLR, SIRI, and mortality outcomes, adjusted for demographic, socioeconomic, and health-related covariates. Additional CBC-derived biomarkers (PLR, dNLR, MLR, SII) were analysed, and mediation analysis assessed albumin's role as a partial mediator of mortality. RESULTS: Over a median follow-up of 116 months, 263 deaths occurred, including 68 from cardiovascular causes. Elevated NLR, NMLR, and SIRI were significantly associated with increased risks of all-cause and cardiovascular mortality. SIRI emerged as the strongest predictor, with adjusted hazard ratios (HRs) of 1.65 (95% CI, 1.23-2.22) for all-cause mortality and 3.18 (95% CI, 1.83-5.53) for cardiovascular mortality. Albumin partially mediated the relationship between SIRI and all-cause mortality (12.1%). CONCLUSION: Elevated NLR, NMLR, and SIRI are associated with increased mortality risks in respiratory sarcopenia, with SIRI demonstrating the highest predictive power. Integrating SIRI into clinical assessments may aid in identifying high-risk patients, allowing for targeted interventions.