Aims: The aim of the study is to explore the relationship between systemic inflammatory response index (SIRI) and impaired cardiorespiratory fitness (CRF) in hyperuricemic population. Methods: This study was a cross-sectional study. We used data from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2004 and screened the population by exclusion criteria. SIRI was calculated from the peripheral blood routines of participants and CRF was calculated from the heart rate and oxygen consumption of participants during the exercise test. CRF was graded according to age and gender. Baseline characteristics of the participants were first calculated. Subsequently, SIRI was grouped into quartiles for weighted logistic analysis. Finally, subgroup analysis was performed to explore the relationship between SIRI and impaired CRF in different populations. Result: Among the 1147 participants in this study, SIRI was an independent risk factor for impaired CRF and the correlation became stronger as SIRI levels increased in hyperuricemic population. In hyperuricemic participants aged less than 20 years, SIRI was positively correlated with impaired CRF in both males and females. In hyperuricemic participants aged 20-49 years, SIRI and impaired CRF were positively correlated in males but negatively correlated in females. SIRI was positively associated with impaired CRF in hyperuricemic participants with metabolic syndrome. Conclusion: SIRI is an independent risk factor for impaired CRF in hyperuricemic population. In the future, SIRI should be applied to impaired CRF prediction models.