Delirium is an acute cognitive disorder caused by a variety of factors which lead to cerebral cortical dysfunction. At present the studies on the pathophysiology of delirium is still very few. But studies on serum biomarker of delirium can help to elucidate the pathophysiological mechanism of delirium, and the studies are significant for delirium diagnosis, severity classification and prediction of long-term outcome. This review examines three major groups of delirium related serum biomarkers: ① risk markers: those that are present or elevated prior to disease onset, including serum chemistries, genetic markers and so on; ② disease markers: those markers elevate with delirium onset and fall when delirium recovery, including acetylcholine and serum anticholinergic activity, serotonin, serum amino acids, and melatonin, interleukin, C-reactive protein; and ③ end products: those that rise in proportion to the consequences of disease, including S-100ß and neuron specific enolase. The three markers mentioned above are helpful to further investigate the mechanism of delirium.