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Introduction: The combination of diabetic ketoacidosis, hypertriglyceridemia, and pancreatitis represents a critical clinical conundrum, carrying approximately 2.8 times the odds of mortality compared to pancreatitis alone. In severe cases, lipemic serum can significantly interfere with standard laboratory assays, complicating diagnosis and management. We hereby present one such case wherein evidence-based examination, clinical judgment, and shared decision-making became the cornerstones of management in light of unreliable laboratory values. Description: A 35-year-old male was admitted to the ICU for management of diabetic ketoacidosis and hypertriglyceridemia-induced pancreatitis (TG >8921 mg/dL). Initial labs showed glucose 529 mg/dL, bicarbonate 15 mmol/L, sodium 120 mmol/L, calcium 2.1 mg/dL, and physiologically implausible liver enzymes (AST –4 U/L, ALT < 6 U/L) due to lipemic interference. Initial management was IV hydration, IV insulin, analgesia, and fibrates. Laboratory reliability remained a challenge: critical values such as calcium (1.8 mg/dL) and phosphate (0.1 mg/dL) were inconsistent with physical findings. Serum osmolarity could not be reliably calculated and therefore, tachycardia, BP, and ICU intake/output charting were used to assess volume status. Metabolic monitoring was delayed by the need for ultracentrifugation. The disappearance of Kussmaul breathing by day 2 indicated a decreased post-test probability of acidosis. Electrolytes were replaced conservatively, considering likely spurious hypocalcemia/hypophosphatemia, with close ECG and clinical monitoring. The patient was counseled daily on the standard of care, case-specific limitations, and the adapted management approach. By day 6, his triglycerides had dropped to < 1000 mg/dL and lab tests were increasingly accurate. He was transitioned to subcutaneous insulin and transferred to the floors with resumption of a diet. Discussion: This case describes the complexity introduced by lipemia in critical care. Even in the setting of unreliable labs, Evidence-based physical examination and utilization of preexisting clinical tools can be used to formulate and execute an informed plan. Through shared clinical decision making, we achieved a favorable outcome.