This study aimed to evaluate the therapeutic plasma exchange (TPE) procedures performed in our pediatric intensive care unit (PICU) and to review the relevant literature. This retrospective study was conducted between 2020 and 2024. Forty-nine patients who received TPE at any point during their PICU stay were included. The groups were categorized as survivors and non-survivors. Of the 49 cases, 71.4% were male, with a median age of 54 months (range 20-135 months). A total of 274 TPE sessions were performed. The three most common indications for TPE were sepsis, trauma induced multiple organ dysfunction syndrome/disseminated intravascular coagulation, and neurological diseases. The non-survivor group had higher rates of chronic illness (p<0.001), pediatric risk of mortality score III, and pre- and post-procedure vasoactive inotropic scores (p=0.005, p<0.001, and p<0.001, respectively). The use of invasive mechanical ventilation and continuous renal replacement therapy (p=0.005, p<0.001, respectively), as well as TPE in cases with sepsis (p<0.001), were more frequent in non-survivors. The most common complication during the procedures was hypotension (9.9%). Sepsis remains the most frequent indication for TPE in PICUs. Although the most common complication of TPE in our study was hypotension, there were no life-threatening complications, suggesting it is a safe treatment modality.