Abstract Background Sickle cell disease (SCD) is one of the most frequent inherited diseases in the world. Over the last decades, in high-income countries, an important decrease in mortality have been observed due to the improvement of care. However, children with SCD can become critically ill and require admission in Pediatric Intensive Care Units (PICU). The purpose of this study was to describe the epidemiology of children with SCD admitted to PICU for acute crisis and to identify factors associated with adverse outcome (AO). Methods We conducted a retrospective study in a Tertiary Hospital in France including all consecutive children with SCD admitted to PICU between January 1st, 2009 and December 31, 2019. We collected baseline patient’s characteristics, clinical and biological data as well as treatments and life sustaining therapies used in the PICU. Patients were defined as experiencing AO in case of death during stay and/or need for invasive mechanical ventilation (MV) and/or for non-invasive ventilation (NIV) for more than 3 days and/or need for vasopressors and/or need for renal replacement therapy. Results We included 579 admissions in 395 patients, mainly of SS genotype (90%) with a median age of 9.2 years [5.5–13.4] and a median baseline hemoglobin of 8.0 g/dl (7.5–8.8). The two main reasons for admission were acute chest syndrome (ACS) ( n = 331, 57%) and vaso-occlusive crisis refractory to first line therapy ( n = 99, 17%). Half of patients required NIV and 47 (8%) required MV. The overall length of stay was 3 days [1–4] and seven (1%) patients died during PICU stay.There was a total of 113 (20%) admissions with AO and on multivariable analysis, baseline hemoglobin < 8 g/dL, history of bronchial obstruction and admission for ACS were associated with AO. There was no difference in the proportion of hydroxyurea treatment or exchange transfusion program between patients with AO and the other patients. Conclusions Baseline hemoglobin < 8 g/dL, history of bronchial obstruction and admission for ACS were the strongest risk factors for severe evolution in SCD children admitted to PICU. These factors could be taken into consideration when choosing the adequate therapeutic options.