We describe a 6-year-old boy who presented with massive hemolysis, shock, disseminated intravascular coagulopathy, and acute renal failure after loxosceles envenomation. In this patient, plasma exchange therapy (PEX) successfully cleared the plasma from an initial hemolytic index of 2000 (equivalent to 2 g/dL hemoglobin, where optimetric laboratory evaluation is impossible) to an index of <50 (no detectable hemolysis). This allowed the PICU team to correct his coagulopathy, assess his degree of organ dysfunction, and provide routine laboratory assessments during continuous venovenous hemodiafiltration. After 9 single volume PEX sessions, his hemolysis and coagulopathy had resolved and his plasma had cleared sufficiently to permit routine laboratory assessments without difficulty. Multiorgan system support with an aggressive transfusion strategy, mechanical ventilation, inotropes, and continuous venovenous hemodiafiltration resulted in complete recovery. We conclude that in the presence of overwhelming hemolysis, plasma can become so icteric that optimetric laboratory evaluation is impossible. In this setting, PEX can be used to clear the plasma, restoring the ability to perform routine laboratory assessments.