Background: Asthma severity is influenced by various immunomodulators; however, the specific roles of thyroid hormones and endothelin in childhood asthma in the South Indian population remain unexplored. Purpose: This study investigated the impact of thyroid hormone and endothelin levels on asthma control among children in South India. Methods: We divided 90 subjects aged 10–15 years into 3 groups as categorized by the Global Initiative for Asthma guidelines: 30 healthy children, 30 patients with well-controlled asthma, and 30 patients with poorly controlled asthma. Fasting blood samples were collected to analyze endothelin levels and thyroid function. Pulmonary function tests were performed using a portable spirometer to assess forced expiratory volume in 1 second (FEV<inf>1</inf>), forced vital capacity (FVC), and the FEV<inf>1</inf>/FVC ratio. Results: Thyroid-stimulating hormone (TSH) levels were significantly elevated in the well-controlled (4.66±1.91 mIU/L) and poorly controlled (6.51±4.04 mIU/L) asthma groups versus the control group (P<0.001). Similarly, endothelin levels showed a marked increase (4.65±0.38 pg/ mL vs. 18.51±6.13 pg/mL), with the poorly controlled group exhibiting the highest levels (P<0.001). A strong negative correlation was observed between FEV<inf>1</inf>/FVC% and serum endothelin levels (r=-0.76) on a Pearson correlation analysis. Conclusion: This study revealed a strong association between endothelin levels, the FEV<inf>1</inf>/FVC ratio, and TSH levels. These findings suggest that serum endothelin level could serve as a potential surrogate marker of asthma severity. © 2025 Elsevier B.V., All rights reserved.