Objective Otosclerosis is a localized metabolic bone disease of the otic capsule with an inflammatory component. This study investigated whether otosclerosis is associated with alterations in systemic inflammatory indices, namely the Neutrophil-to-Lymphocyte Ratio (NLR) and the Systemic Immune-Inflammation Index (SII).Materials and methods This retrospective case-control study included 52 patients with otosclerosis who underwent stapedotomy and 50 control subjects who underwent septoplasty for isolated nasal septal deviation between January 1, 2023 and January 1, 2024. Preoperative venous blood samples were obtained within 7 days before surgery, between 08:00 and 10:00 a.m. after overnight fasting. Complete blood counts were analyzed using an automated hematology analyzer (UniCel DxH 800, Beckman Coulter, USA). SII was calculated as (platelet & times; neutrophil)/lymphocyte, and NLR as neutrophil/lymphocyte. Group comparisons, multivariable logistic regression (adjusted for age and sex), and ROC curve analyses were performed.Results SII was significantly higher in the otosclerosis group than in controls (599.1 +/- 154.3 vs. 503.5 +/- 114.8; p = 0.041). NLR was numerically higher in otosclerosis (2.14 +/- 0.8 vs. 1.89 +/- 0.6) but did not reach statistical significance (p = 0.107). Individual components showed no significant between-group differences in neutrophil count (4.96 +/- 1.53 vs. 4.73 +/- 1.99 & times; 103/mu L; p = 0.516) or platelet count (279.22 +/- 55.71 vs. 266.63 +/- 74.98 & times; 103/mu L; p = 0.337), while lymphocyte count was significantly lower in otosclerosis (2.31 +/- 0.65 vs. 2.50 +/- 0.84 & times; 103/mu L; p = 0.019). In multivariable analysis, SII (per 100-unit increase) remained independently associated with otosclerosis (OR = 1.24, 95% CI: 1.00-1.53; p = 0.047). ROC analysis demonstrated moderate discrimination for SII (AUC = 0.658, 95% CI: 0.501-0.815).Conclusion SII was independently associated with otosclerosis, suggesting a subtle systemic immune-inflammatory signature. Given the borderline significance and moderate ROC performance, these findings should be interpreted as exploratory and require confirmation in larger prospective cohorts.