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To measure changes in end-tidal carbon dioxide levels (ETCO2) during sedation/analgesia in pediatric patients and to describe ETCO2 changes associated with different sedation strategies.This was a prospective, observational patient series in an urban pediatric emergency department (PED). Participants included 106 children with a mean age of 6.8 years. (range 1.2–16.6 years). Sedation/analgesia was given for fracture reduction (55%), laceration repair (37%), abscess incision and drainage (4%), and lumbar puncture (LP) (4%). Medications included fentanyl, morphine, ketamine, and midazolam. Continuous ETCO2 waveforms were recorded via a Capnogard® ETCO2 Monitor. Oxygen saturation was recorded using a Nelcor N-200 pulse oximeter. Recording began prior to sedation and continued until the patient was awake or when it was necessary to remove the patient from the monitor for further medical care. Each record was analyzed for peak ETCO2 and averaged over five consecutive breaths, before and after the administration of medications. The main outcome measure was the change in ETCO2 levels.The mean increase in ETCO2 was 6.7 mmHg (P⊂ 0.00001; range: +0.16 to +22.3). ETCO2 increased by 3.2 mmHg (95% CI = 2.2–4.2) for midazolam alone, 5.4 mmHg (95% CI = 4.5–6.4) for midazolam and ketamine, and 8.8 mmHg (95% CI = 7.4–10.2) for midazolam and opiate. Two patients had transient SpO2 desaturations below 93%, which corrected with stimulation.Commonly used agents for pediatric sedation result in significant increases in ETCO2. ETCO2 is a useful adjunct in assessing ventilation and may serve as an objective research tool for assessing different sedation strategies.