Chronic adenotonsillitis is a common condition that significantly impacts quality of life, often necessitating surgical intervention through adenotonsillectomy. While the procedure is primarily performed to relieve airway obstruction and reduce infection recurrence, its systemic effects on inflammation and immune response remain underexplored. This study evaluates the impact of adenotonsillectomy on Neutrophil-to-Lymphocyte Ratio (NLR) and Antistreptolysin O (ASO) titres, which serve as biomarkers for systemic inflammation and streptococcal infection, respectively. A prospective observational study was conducted on 100 patients aged 5–18 years diagnosed with chronic adenotonsillitis and scheduled for adenotonsillectomy at a tertiary care center. Preoperative blood samples were collected to assess NLR and ASO titres, followed by repeat measurements at 1, 3, and 6 months postoperatively. Statistical analysis was performed using paired t-tests, with a significance threshold of p < 0.05. The mean preoperative NLR was 2.02, which significantly declined postoperatively to 1.70 at 1 month, 1.56 at 3 months, and 1.50 at 6 months (p < 0.001). ASO titres significantly decreased from 682.19 IU/mL preoperatively to 355.02 IU/mL at 1 month, 211.77 IU/mL at 3 months, and 75.09 IU/mL at 6 months (p < 0.001). These findings suggest a substantial reduction in systemic inflammation and streptococcal antigenic burden following adenotonsillectomy. Adenotonsillectomy effectively reduces systemic inflammation and streptococcal antigenic load, as evidenced by significant postoperative reductions in NLR and ASO titers. These findings reinforce the role of adenotonsillectomy beyond symptom relief, highlighting its broader immunological benefits. © 2025 Elsevier B.V., All rights reserved.