Objective: To compare the effects of high concentration to titrated oxygen therapy (HCOT) on transcutaneous carbon dioxide (PtCO2) level in pediatric asthma exacerbation. Titrated oxygen therapy (TOT) in acute asthma will avoid a rise in PtCO 2 in the pediatric population. Method: The study design is a prospective, randomized, clinical trial comparing HCOT (maintain SpO2 92-95%) while being treated for asthma exacerbation in the emergency department (ED). Inclusion criteria: 2 to 18 years, previously diagnosed asthma with acute exacerbation (asthma score >5). PtCO2 and asthma scores were measured at 0, 20, 40, 60 minutes and then every 30 minutes until disposition decision. The primary outcome was a change in PtCO 2. Secondary outcomes were admission rate and change in asthma score. Results: A total of 96 patients were enrolled in the study with a mean age of 8.27 years; 49 in HCOT and 47 in the TOT group. The 0 minute PtCO2 was similar (35.33 + 3.88 HCOT vs 36.66 + 4.69 TOT, P = 0.13); whereas, the 60 minutes PtCO 2 was higher in the HCOT (38.08 + 5.11 HCOT vs 35.51 + 4.57 TOT, P = 0.01). The asthma score was similar at 0 minute (7.55 + 1.34 HCOT vs 7.30 + 1.18 TOT, P = 0.33); whereas, the 60 minutes asthma score was lower in the TOT (4.71 + 1.38 HCOT vs 3.57 + 1.25 TOT, P = 0.0001). The rate of admission to the hospital was 40.5% in HCOT vs 25.5% in the TOT (P = 0.088). Conclusions: HCOT in pediatric asthma exacerbation leads to significantly higher carbon dioxide levels, which increases asthma scores and trends towards the increasing rate of admission. Larger studies are needed to explore this association.