Background: Sinusoidal obstruction syndrome (SOS), a serious complication after hematopoietic cell transplant (HCT), is associated with multi-organ dysfunction (MOD) and a high mortality rate. In severe cases, continuous kidney replacement therapy (CKRT) is initiated to manage fluid overload (FO) and acute kidney injury. Studies that evaluate the use of CKRT in this population are lacking. The aim of our study was to assess the outcome of critically ill children with severe SOS post HCT who received CKRT. We also sought to assess factors associated with survival and liberation post CKRT. Procedure: Retrospective review of all children admitted to the intensive care unit (ICU) with SOS post HCT who received CKRT from January 2010 to August 2022. Results: Among the 53 children who received CKRT post HCT, 13 had severe SOS. The median age was 6 years; 62% were males, and most (77%) received allogeneic HCT. In this cohort, 92% required respiratory support and 85% required vasopressor support. The ICU survival rate was 62%. Survivors experienced lower cumulative FO on the 2 days following CKRT initiation (-4.2% in survivors versus -0.5% in non-survivors, p=0.07). Higher urine output on D1 and D2 after discontinuation of CKRT was associated with successful liberation. Conclusions: In this study of post-HCT children with SOS and MOD who received CKRT, 62% survived until ICU discharge. This survival rate is encouraging as it approximates the survival rates of general pediatric cohorts treated with CKRT. Reducing FO after initiation of CKRT can improve survival in these children.