To evaluate the acceptability and safety profile of nocturnal long-term oxygen therapy (LTOT) in children with sickle cell disease (SCD) and chronic hypoxaemia. Retrospective cohort study. Children with SCD who started LTOT from 2014 to early 2019 in two tertiary hospitals in London, UK were retrospectively enrolled. Patients who started disease-modifying therapies <12 months before LTOT or while on LTOT were excluded. Minor and major adverse events during LTOT were reported. Laboratory and clinical data, transcranial Doppler (TCD) scans and overnight oximetry studies performed at steady state within 12 months before and after starting LTOT were compared. Nineteen children (10 males; median age 12 years, range 6-15) were included. Nearly half of them (9/19; 47%) were on hydroxyurea at baseline. No child discontinued LTOT because of intolerance or poor adherence. No major adverse events were reported. Laboratory data did not show significant changes in haemoglobin and reticulocyte count after 1 year of follow-up. No statistically significant change in the incidence of vaso-occlusive pain events was noted (median annual rate from 0.5 to 0 episode per patient/year; p=0.062). Overnight oximetry tests performed while on LTOT showed improvements in all oxygen saturation parameters (mean overnight and nadir SpO , % of time spent with SpO <90%) compared with the baseline. LTOT is a safe and feasible treatment option for children with SCD and chronic hypoxaemia.