Background <p>Metabolic decompensation is life-threatening in children with organic acidemia (OA). This study aims to evaluate the efficacy of continuous renal replacement therapy (CRRT) in treating patients with OA complicated by decompensated metabolic acidosis in pediatric intensive care units (PICU) and to explore its impact on organ function impairment associated with this condition.</p> Methods <p>Data of children with OA developed decompensated metabolic acidosis admitted to PICU between 2013 and 2024 were collected and retrospectively analyzed. The patients were divided into two groups: the CRRT treatment group (admitted after 2019) and the conventional treatment group (admitted before 2019).</p> Results <p>Forty-six patients were included in the study. After 24 hours of CRRT therapy, there was a significant decrease in levels of lactic acid, plasma ammonia, blood urea nitrogen, creatinine, troponin, myoglobin and neuron-specific enolase (NSE) compared to the conventional treatment group. After 48 hours of CRRT therapy, alanine aminotransferase and aspartate aminotransferase levels decreased in comparison with the conventional treatment group (<i>p</i> &lt; 0.05). After 5 days of therapy, a significant decline in NSE persisted in the CRRT group compared to the conventional treatment group (<i>p</i> &lt; 0.05). In the conventional group, organ injury biomarkers increased at 24 hours and gradually declined over time, whereas no elevation of these biomarkers was observed in the CRRT group. The duration of mechanical ventilation and the length of stay in the PICU were significantly shorter in the CRRT group (<i>p</i> &lt; 0.05).</p> Conclusions <p>In patient with OA complicated by decompensated metabolic acidosis, the treatment combined with CRRT can efficiently remove metabolites, thereby avoid neuron and the major organs from further injury. Application of CRRT can help these patients recover earlier from the metabolic crisis.</p>