Introduction: Rhabdomyolysis is a serious condition that can cause acute kidney injury (AKI), compartment syndrome, severe metabolic and electrolyte derangement leading to arrhythmias, and even death. Total plasma exchange (TPE) has been used as a treatment modality to clear myoglobin, but the evidence is limited. In this study, we aim to investigate the use of TPE in critically ill rhabdomyolysis patients.Methods: We retrospectively chart reviewed adult patients admitted to the intensive care unit (ICU) with a diagnosis of rhabdomyolysis between 2012 and 2021. We dichotomized patients into two groups based on whether TPE was used or not in addition to standard care. PRISMA machines with TPE2000 filters and either 5% albumin or fresh frozen plasma were used in the TPE group.Results: The patients' age ranged from 23 years to 87 years (mean 49.4, SD 18.1), and 51% were male. Initial creatinine ranged from 0.6 to 16mg/dL (mean 3.4, SD 2.7), creatinine phosphokinase (CPK) from 403-93,232 U/L, and myoglobin from 934 to >20,000. The Sequential Organ Failure Assessment (SOFA)scores on admission ranged from 6 to 17 (mean 7.23, SD 3.40). Overall, 28.78% (N=19) of the patients received therapeutic plasma exchange. The overall mortality in our study was 31.9%, with the length of ICU stay ranging from 1-25 days (mean 7.10, SD 5.91) among survivors. Older age and the presence of shock were predictive of mortality in univariate and multivariate analyses. There was no statistically significant association in mortality between the TPE and non-TPE groups (36.84% in TPE vs. 36.17% in the non-TPE group, OR 0.7209, p=0.959). Only two patients in the non-TPE group developed CKD/ESRD on long-term follow-up.Conclusion: Our study showed that TPE administration in critically ill patients with rhabdomyolysis did not improve mortality or length of ICU stay. Further studies are required to elucidate its indication and effect on long-term renal outcomes.