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Abstract Intracranial aneurysms are increasingly recognized as inflammatory vascular disorders rather than purely structural lesions. Metabolic factors such as hyperhomocysteinemia and systemic inflammatory markers may contribute to endothelial dysfunction and aneurysm instability, but their relationship with clinical severity and rupture status remains incompletely understood. To evaluate serum homocysteine and high-sensitivity C-reactive protein (hs-CRP) levels in patients with intracranial aneurysms and examine their association with aneurysm location, rupture status, and established clinical grading systems. In this cross-sectional observational study, patients aged > 18 years undergoing surgical treatment for intracranial aneurysms were included. Preoperative serum homocysteine and hs-CRP levels were measured. Clinical severity was assessed using Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), and modified Fisher's grading systems. Statistical analyses included analysis of variance, Kruskal–Wallis' testing, effect size estimation (η2), Spearman's correlation, rupture subgroup analysis using Cohen's d, ordinal logistic regression, and multivariate linear regression. The study included 79 patients with complete biochemical and radiological data. The mean serum homocysteine level was 11.37 ± 5.61 µmol/L, and the mean hs-CRP level was 57.90 ± 47.18 mg/L. No statistically significant differences in biomarker levels were observed across aneurysm locations (p > 0.05). Effect size analysis demonstrated small-to-moderate associations for homocysteine (η2 = 0.058) and moderate associations for hs-CRP (η2 = 0.102). No statistically significant differences in biomarker levels were observed between ruptured and unruptured aneurysms. Ordinal logistic regression demonstrated a statistically significant inverse association between hs-CRP levels and WFNS grade (β = −0.078, odds ratio = 0.92), indicating that higher hs-CRP levels were associated with lower WFNS grades. However, the strength of association was modest. Although hs-CRP demonstrated a modest inverse association with WFNS grade, neither homocysteine nor hs-CRP levels were significantly elevated compared with matched controls. These findings suggest limited discriminatory value of circulating biomarkers in aneurysm pathology.