Objective: Acute pancreatitis is an inflammatory disorder of the pancreas with diverse etiologies, including rare drug-induced causes such as propofol. Propofol-associated acute pancreatitis has been linked to hypertriglyceridemia; however, causal attribution is particularly challenging in patients with chronic kidney disease, due to metabolic disturbances and overlapping clinical features. Case: We report the case of a 49-year-old female with end-stage chronic kidney disease admitted with septic shock requiring mechanical ventilation and continuous sedation with propofol infused at 70 mg/h. After 8 days of therapy, she developed progressive hypertriglyceridemia followed by clinical and biochemical findings consistent with acute pancreatitis. Common etiologies were excluded, and the temporal relationship supported a probable adverse drug reaction. Discussion/Conclusions: This case highlights the diagnostic and causal complexity of acute pancreatitis in critically ill patients with advanced chronic kidney disease and underscores the importance of vigilant metabolic monitoring and multidisciplinary medication review during propofol therapy.