Extracorporeal photopheresis (ECP) is a vital therapeutic option for pediatric patients with immune-mediated conditions. However, the high extracorporeal volume (ECV) involved in ECP poses a risk of hypovolemia, often necessitating red blood cell (RBC) priming to maintain hemodynamic stability. This study evaluates a conservative approach to ECP without RBC priming in pediatric patients, aiming to reduce allogenic blood exposure. A retrospective review of 16 ECP procedures across 3 pediatric patients with ECV exceeding 15% of total blood volume (TBV) found no significant adverse events or hemodynamic instability. The absence of RBC priming did not result in any documented complications. These findings suggest that conservative blood priming can safely reduce allogenic blood exposure in pediatric ECP, potentially minimizing transfusion-related risks. Further research is needed to establish guidelines for patient selection and monitoring during non-prime ECP in pediatric populations.