BACKGROUND: Immune-Inflammation plays a crucial role in the pathogenesis of diabetic kidney disease (DKD), but the exact assessment of indicators are undefined. Our paper examined the link between Systemic immune-inflammation index (SII) and mortality risk in DKD, and explore the effect of sex disparities on it. METHODS: Data of DKD patients from the National Health and Nutritional Examination Surveys (NHANES) data (1999-2018) were studied and the causes of mortality were identified from NHANES-related files. A Weighted Cox model evaluated hazard ratios (HR) for all-cause, cardiovascular and cardio-cerebrovascular mortality, and these associations were visualized by smoothing curves. RESULTS: The average level of SII was 634.20 (10ˆ3/uL). 1,283 deaths were recorded during 273,422 person-months, of which, 396 died form cardiovascular and 461 form cardio-cerebrovascular. Higher SII levels in the Q5 quintile were significantly associated with the increased mortality (P <
0.01). Trends in SII levels showed an increased risk of all-cause mortality at levels >
697 (10ˆ3/uL), cardiovascular risk at levels >
717.8 (10ˆ3/ uL), and cardio-cerebrovascular risk at levels >
650.0 (10ˆ3/uL). In male, the mortality would increase with the SII levels of 500-660 (10ˆ3/ uL), while it was 700-760 (10ˆ3/uL) in female. CONCLUSIONS: A significant association between higher SII levels and increased risks of all-cause, cardiovascular and cardio-cerebrovascular mortality in DKD patients. In addition, though male have lower SII levels, their mortality was higher than that of female.