Objective: To investigate the association of high-sensitivity C-reactive protein (hs-CRP) with insulin resistance and metabolic syndrome among obese patients attending a tertiary care hospital in Karachi, Pakistan. Methods: A cross-sectional study was conducted from January to June 2025 at a tertiary care hospital in Karachi. Seventy-five obese individuals (BMI ≥30 kg/m²) aged 20–60 years were enrolled. Fasting blood samples were analyzed for hs-CRP, fasting plasma glucose, insulin, lipid profile, and other metabolic parameters. HOMA-IR was calculated. Metabolic syndrome was diagnosed based on IDF criteria. Results: The mean age of participants was 43.2 ± 9.8 years. Elevated hs-CRP (>3 mg/L) was found in 61.3% of participants. Patients with high hs-CRP had significantly higher HOMA-IR scores (p<0.001). Metabolic syndrome was present in 68% of subjects, and mean hs-CRP levels were significantly higher in individuals with metabolic syndrome (p<0.001). Positive correlations were found between hs-CRP and fasting glucose, triglycerides, waist circumference, and HOMA-IR. Conclusion: High-sensitivity CRP levels were strongly associated with insulin resistance and the presence of metabolic syndrome. hs-CRP may serve as an early, accessible biomarker for identifying patients at risk of metabolic complications.