<p>Abstract</p> <p>Background</p> <p>Respiratory syncytial virus (RSV) is one of the most important causes of pediatric hospital admissions in the developed world. The ribonuclease Dicer is an important regulator of gene expression and cellular function via RNA interference, and may also have anti-viral functions. A previous microarray analysis of the cord blood of 5 patients with RSV disease suggested downregulation of <it>Dicer</it>. In order to further investigate whether reduced <it>Dicer </it>expression can predispose newborns to RSV disease, we have analyzed the gene expression of <it>Dicer </it>in the cord blood of 37 infants with confirmed RSV disease.</p> <p>Methods</p> <p>The cord blood of 2108 newborns was collected. 51 had a positive nasopharyngeal aspirate for RSV <1 year, and were grouped according to disease severity. 37 had sufficient cord blood RNA of good quality. <it>Dicer </it>gene expression was assessed by qPCR analysis of cord blood using a TaqMan low-density array and compared to control infants who did not present with RSV disease using the Mann-Whitney test.</p> <p>Results</p> <p>There was significant downregulation of <it>Dicer </it>in the severe disease group: relative quantity 0.69 (95% CI: 0.56 - 0.87), p = 0.002. There was no significant downregulation in the mild disease group.</p> <p>Conclusions</p> <p>We demonstrate reduced <it>Dicer </it>expression in the cord blood of infants with severe RSV disease, prior to RSV exposure. We theorize that this may predispose to RSV disease by disruption of leukocyte gene regulation or direct anti-viral RNA interference mechanisms.</p