Background: Splenic dysfunction in children with sickle cell disease (SCD) increases the risk of serious bacterial infections; therefore, families are instructed to seek medical care in the presence of fever. Recurrent hospital admissions of patients with SCD cause financial and resource burdens on caregivers and the healthcare system, contributing to a lower quality of life in this patient population. Recent studies have documented a reduction of the incidence of bacterial infections among these patients managed on an outpatient basis with no association of increased morbidity and mortality. We decided to establish a partnership between our pediatric hematology/oncology division and pediatric emergency medicine division to initiate an algorithm to identify low risk patients eligible for outpatient management. Procedure: We conducted a retrospective review of patients with SCD less than 18 years of age, followed at the Comprehensive Care Sickle Cell Center at the Medical University of South Carolina (MUSC), who presented to our Pediatric Emergency Department (ED) with a temperature ≥ 101°F from July 1st 2018 to June 30th 2020. Results: Mean length of stay and age at admission were nearly equal between pre- and post-implementation of the algorithm. The admission rates from the study for were 55.2% and 43.6% pre- and post-implementation, respectively. Patients revisited the ED within 72 hours in 6.7% of patients in pre-implementation and 5.9% of patients in post-implementation. There were no patient deaths. Conclusions: Our pathway helps to standardize the treatment of febrile pediatric patients with SCD and safely decreases hospital admissions.