Background: Management of refractory pain in pediatric sickle cell disease (SCD) and oncology is reliant on opioids though high opioid dosing increases side effects and tachyphylaxis. We introduced low dose ketamine infusion (LDKI) to our inpatient unit to determine if LDKI was safe and tolerable. We subsequently hypothesized that LDKI would improve pain scores but not decrease opioid utilization. Procedure: We retrospectively reviewed inpatients from LDKI initiation in March 2014 through October 2017, analyzing each patient’s first admission with LDKI. The day prior to LDKI initiation was compared with the day of LDKI initiation and two subsequent days in regard to cumulative daily opioid utilization, vital signs and pain scores. For patients with SCD, the LDKI admission was compared with up to three admissions in the prior year for a vaso-occlusive event. Results: Nineteen patients (12 oncology, 7 SCD) with a median age of 14.6 years received LDKI for a median of 6 days at a median initial dose of 0.06 mg/kg/h (1.1 mcg/kg/min). There was no change in pain scores, heart rate or opioid utilization when comparing the day prior to LDKI initiation with subsequent days. No patient discontinued LDKI due to intolerability. For patients with SCD, there was a median 32% reduction in cumulative pain scores when comparing the LDKI admission with prior admissions. Conclusions: LDKI is well tolerated and may be a viable option for refractory pediatric cancer- and sickle cell-related pain. Future study is required to further delineate appropriate dosing and patients most likely to benefit.