Four patients were recently seen at our institution presenting with severe hypobicarbonatemia and elevated anion gap on serum specimens processed by an autoanalyzer using enzymatic reactions. Arterial blood gas values in each case revealed no significant acid-base disturbance and a marked discordance between arterial blood gas calculated bicarbonate levels and those reported on the basic metabolic panel. All patients had profound hyperlipidemia (triglycerides > 3,500mg/L), and ultracentrifugation of one patient’s serum corrected the discordance.