The risk of opioid use disorder among patients with sickle cell disease who are treated with chronic opioids remains unclear, but the complications associated with opioid use and overdose can be accentuated in those with sickle cell disease. In this case report, we describe a 13-year-old girl with sickle cell disease who presented to the emergency department after a morphine overdose causing renal infarction, acute kidney injury, acute respiratory distress syndrome, and posterior reversible encephalopathy syndrome.