BACKGROUND Although many serologic markers have been suggested for diagnosis of necrotizing enterocolitis, there is little consensus on which of these is potentially clinically useful. Our aims were (i) to systematically review circulating markers that are potentially useful in the diagnosis of NEC and (ii) to compare the relative performance of each serologic marker of NEC by pooling estimates of marker accuracies and presenting their combined diagnostic accuracies. METHODS We undertook a systematic review of the literature to identify studies that reported serologic markers at the time of diagnosis of necrotizing enterocolitis. Where possible, we constructed 2-by-2 tables of diagnostic accuracy from each article, if 2 or more studies investigated the same test, their results were meta-analyzed by pooling estimates of sensitivity, specificity, likelihood ratio for positive index test (LR+), likelihood ratio for negative index test (LR-), diagnostic odds ratio, and their corresponding 95% confidence intervals. RESULTS Twenty-five articles provided information on serology at the time of diagnosis of necrotizing enterocolitis. Of these, it was possible to construct diagnostic accuracy tables from 16 articles and to combine data from studies that used C-reactive protein, intestinal fatty acid binding protein, and platelet-activating factor. Of these C-reactive protein was a sensitive but nonspecific marker for necrotizing enterocolitis, whereas platelet-activating factor and intestinal fatty acid binding protein were both sensitive and specific. CONCLUSIONS Most serologic markers of necrotizing enterocolitis have been used in too few studies to evaluate their use. Of those tests that have been tested repeatedly, platelet-activating factor and intestinal fatty acid binding protein are potentially useful, although their use must be further tested in larger prospective studies.