Background: Short bowel syndrome is a disorder with several complications such as malnutrition and failure of drug therapy. Treatment with opioids is needed in many patients, and oral medication is preferred. However, optimal dosing is a difficult task as current guidelines are based on an intact gastrointestinal tract. Hence, the aim of this explorative case study was to assess the pharmacokinetics of orally administered oxycodone in patients with short bowel syndrome. Methods: Six patients with short bowel syndrome were administered 10 mg oral solution oxycodone after an overnight fast. Oxycodone plasma concentrations were determined over a 6-hour period. Pharmacokinetic profiles were visually inspected. Pharmacokinetic parameters: maximum plasma concentration, time of maximum concentration and area under the curve were calculated. Data were also compared to mean values obtained in healthy participants. Results: A clinically relevant concentration of oxycodone was found in all patients, although with large inter-individual variation. The absorption fraction tended to correlate positively with total intestinal length. Additionally, preservation of some or the entire colon seemed further to increase the absorption fraction. Time of maximum concentration varied from 30 min to approximately 90 min. Conclusions: Oxycodone is absorbed in a clinically relevant extent in patients with short bowel syndrome, but bioavailability varies greatly between patients, which shall be taken into consideration. Absorption is related to functional small intestinal length, but preservation of colon is also beneficial. Still, optimal therapeutic dosing must be individualized, and other factors such as those related to malnutrition and motility shall also be taken into consideration.