Marginal zinc (Zn) deficiency is presumed to be prevalent throughout the world. Currently, there is no reliable biomarker of Zn status. Although plasma Zn concentration is routinely used, its reliability is questionable due to tight homeostatic regulation. Herein, we utilized microarray analysis of monocytes isolated from mice fed diets differing in Zn content to identify potential biomarkers for marginal Zn deficiency in humans. Weanling male Swiss‐Webster mice were fed a diet differing only in Zn content (n=10 mice/diet) for 30 days: supplemented (180 mg Zn/kg diet), control (30 mg Zn/kg diet) and marginally low (15 mg Zn/kg diet). Weight gain, food intake, and serum Zn levels were not affected. Zn concentration in liver, small intestine, spleen, kidneys, and muscle were reduced in mice fed a Zn deficient diet. Microarray analysis revealed 433 genes whose mRNA expression differed significantly between diet groups. Of 127 annotated genes there was an effect of Zn intake on the expression of 24 genes (p<0.05) including RNA‐binding proteins, mitochondrial proteins, and protein kinases. In conclusion, our data suggest that these novel genes may be useful for establishing a gene signature for Zn nutrition, and studies are under way to validate their usefulness in assessing Zn status in human populations. Supported by Intramural Funds to SLK.