Objective. To determine the effect of activated charcoal (AC) on acetaminophen (APAP) absorption kinetics when administered at 1, 2, or 3 h after combined oral overdose with oxycodone. Methods. IRB-approved, prospective cross-over study of nine healthy human volunteers ingesting 5 g of APAP + 0.5 mg/kg of oxycodone on each of four study days. On the control day, subjects received no AC. On the remaining study days, subjects ingested 50 g of AC at 1, 2, or 3 h after drug ingestion. We measured serum APAP concentration hourly from 0 through 8 h and compared basic non-compartmental pharmacokinetic parameters. Results. Compared to the control, AC reduced area under the curve by 43% when given at 1 h (p 0.0001), 22% when given at 2 h (p = 0.02), and 15% when given at 3 h (p = 0.26). AC at 1 h resulted in a 25% reduction in peak APAP concentration from 48.6 to 36.3 mcg/mL (p = 0.012) with no significant difference when given at 2 or 3 h. There was no significant difference in elimination half-life among the four study days. Conclusion. The effect of AC rapidly declines between 1 and 3 h after combined oral overdose of APAP and oxycodone. AC is unlikely to be beneficial at or beyond 2 h after an overdose of acetaminophen and oxycodone.