There is increasing clinical interest in the measurement of serum total sialic acid (TSA). There are a number of methods available but with little data suggesting the preferred technique. We evaluated three serum sialic acid assays: the Warren assay, the Svennerholm assay, and a commercially available enzymatic method. The analytical performances of the three assays were similar, except that the enzymatic assay had a greater analytical range than the other assays and better precision at low and high serum sialic acid concentrations. The enzymatic assay was readily automated for use on a Cobas Bio analyser but was substantially more expensive than the other two methods.