Abstract After surgery, in sepsis and various critical illnesses, factors such as severity of the acute phase response, liver dysfunction, and hemodilution from blood loss have cumulative impacts in decreasing cholesterol; therefore, degree of hypocholesterolemia often reflects severity of illness. The direct correlation between cholesterol and several plasma proteins is mediated by the parallel impact of commonly shared determinants. Cholestasis is associated with a moderation of the degree of hypocholesterolemia. In human sepsis, the poor implications of hypocholesterolemia seem to be aggravated by the simultaneous development of hypertriglyceridemia. Cholesterol and triglyceride levels reflect altered lipoprotein patterns, and the issue is too complex and too poorly understood to be reduced to simple concepts; nevertheless, these simple measurements often represent helpful adjunctive clinical tools.