BackgroundOsteoarthritis (OA) is the most prevalent form of arthritis worldwide. Inflammation and nutrition status play crucial roles in the development and progression of OA. The advanced lung cancer inflammation index (ALI) serves as a composite indicator for evaluating inflammation and nutritional status, while the systemic immune inflammation index (SII) is a novel marker for assessing immune-related inflammation. The study aimed to investigate the associations of the ALI and SII with all-cause and cardiovascular mortality among US adults with OA.MethodsA total of 2,602 individuals aged 20 years and above with OA were included in the study from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Participants were categorized into higher or lower ALI and SII groups using cut-off values determined by the maximally selected rank statistics method. The Kaplan-Meier analysis, Cox proportional hazards models, and Fine Gray competing risk regression models were employed to assess the associations between the ALI/SII and mortality in OA patients. Additionally, stratified and subgroup analyses were conducted to enhance the robustness of the findings. Furthermore, time-dependent receiver operating characteristic (ROC) analysis was used to evaluate the predictive capacity of ALI and SII for mortality.ResultsHigher SII levels were associated with a 2-fold increase in the risk of all-cause mortality (HR: 2.00, 95% CI: 1.59–2.52, p < 0.001), whereas individuals with higher ALI in the OA group exhibited a significantly reduced risk of all-cause mortality (HR: 0.49, 95% CI: 0.39–0.60, p < 0.001). Notably, in Model 3, individuals with higher ALI demonstrated a substantially lower risk of cardiovascular mortality (HR: 0.60, 95% CI: 0.44–0.82, p < 0.001). Conversely, in fully adjusted models, those with higher SII experienced a significantly higher risk (HR: 1.83, 95% CI: 1.29–2.60, p < 0.001). The RCS analysis revealed a J-shaped non-linear relationship between SII levels and all-cause mortality (p overall < 0.001; p non-linear < 0.001), and an L-shaped non-linear association between ALI levels and all-cause mortality (p overall < 0.001; p non-linear = 0.002). The time-dependent ROC curves illustrated that ALI and SII displayed a reasonably good and consistent predictive performance for both short- and long-term mortality in OA patients.ConclusionsLower ALI and higher SII values were correlated with increased risks of all-cause and cardiovascular mortality among US adults with OA.