Background: Tuberculosis (TB) treatment efficacy is traditionally assessed through clinical and microbiological evaluations. This study investigates the utility of serial C-reactive protein (CRP) measurements as a biomarker for monitoring treatment response in TB patients. Methods: In this prospective observational study, 204 newly diagnosed TB patients were enrolled from a tertiary care hospital in central India between November 2022 and April 2024. Serum CRP levels were assessed at baseline, 6 months, and treatment completion. Results: A significant decrease in median CRP levels (IQR) was observed in both PTB 32 mg/L (20.25 - 52.75) to 3mg/L (2.275 - 4), p< 0.05 and EPTB patients 30mg/L (14-55) to 3mg/L (2.2-4), p< 0.05 during treatment. Notably, 30% of PTB and 61.7% of EPTB patients required extended treatment beyond 6 months, with median CRP levels remaining elevated (>5 mg/L) at 6 months. Conclusion: Serial CRP measurements demonstrate potential as a biomarker for monitoring TB treatment response, with declining levels correlating with effective treatment. This biomarker may aid in guiding end-of-therapy decisions and optimizing treatment duration.