Red blood cell (RBC) exchanges (RCE) are particularly efficient to treat and prevent complications in patients with sickle cell anemia (SCA). However, the low-weight of young children is a barrier to their use. Spectra Optia is a therapeutic apheresis platform that enables automatic priming to prevent hemodynamic complications in low-weight children. The easiest method is to use albumin for priming, which is allowed by the software. We conducted a retrospective monocenter analysis of the feasibility, safety, and efficacy of albumin priming during RCE (RCE/Alb-primed) in 19 children weighing 12 to 23 kg for a total of 153 sessions. They were treated either on an emergency basis (8 children, 8 sessions), before surgery (2 children, 4 sessions) or as part of a RCE program (9 children, 141 sessions). Indications of RCE/Alb-primed sessions included: (i) an extracorporeal volume of the kit equal to 15% of the child's total blood volume; (ii) a weight of less than 20 kg; or (iii) a weight between 20 and 25 kg with a hematocrit (Hct) of 20% or less. We monitored Grade 2 adverse events (AEs) during the sessions, in extenso decreased blood pressure, increased heart rate and fatigue. Post-apheresis hematocrit and the fraction of cell remaining (FCR) values after RCE were compared to the expected ones. A low incidence of complications was observed in the 153 RCE/Alb-primed sessions with only 1 episodes of transient Grade 2 AEs. Post-apheresis Hct and FCR reached expected values with the RCE/Alb-primed method. In conclusion, RCE/Alb-primed seems to be safe and efficient in young SCA children and should be proposed systematically for curative RCE or prophylactic programs.