Tuberculosis treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol achieves high cure rates but carries hepatotoxicity risks (2-28% globally) and nephrotoxicity, necessitating biochemical monitoring. C-reactive protein (CRP) has emerged as a potential treatment response biomarker, yet longitudinal data from sub-Saharan Africa remain limited. This study characterized biomarker evolution during standard anti-TB treatment in Cameroon. Prospective cohort studyof 45 HIV-negative pulmonary TB patients at Jamot Hospital, Yaoundé (March 2023–September 2025). Participants received WHO-recommended 2HRZE/4HR regimen. CRP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen were measure datbase line (M0), month 2 (M2), and month 6 (M6). Friedman test with Bonferroni- corrected post-hoc comparisons evaluated longitudinal changes. All 45 patients completed treatment; 95.6% achieved microbiological cure. Median CRP declined 50% from baseline to treatment completion (48→24 mg/L), with no change during intensive phase (M0-M2) but significant reduction during continuation phase (M2-M6, p<0.001). No severe hepatotoxicity occurred (0% with ALT >100 U/L); median ALT decreased 31% (26→18 U/L). AST/ALT ratio increased progressively (0.75→1.51), indicating mild rifampicin-induced enzymaticad aptation without clinical sequelae. Creatinine stability confirmed renal safety. Blood urea nitrogen exhibited marked variability, reflecting heterogeneous nutritional status. Systematic CRP monitoringat M0, M2, and M6 provides cost-effective treatment response assessment in resource-limited settings. This first Cameroonian evaluation of longitudinal CRP kinetics demonstrates feasibility of biomarker-guided TB management. Future studies should validate findings in HIV-coinfected populations.