C-type natriuretic peptide (CNP) is a paracrine growth factor critical in endochondral bone growth. Amino-terminal CNP (NTproCNP), measurable in plasma, correlates with growth-plate activity and can be used as a biomarker of growth velocity in children. Because severe inflammation in adults increases CNP, we studied CNP peptides and inflammatory markers in children with acute illness. Forty-two children aged 2 mo to 5 y with acute illness warranting admission to an acute assessment unit were studied. Fifteen age-matched healthy children attending an outpatient clinic served as controls. Venous CNP concentrations were measured at admission, along with markers of acute inflammation (body temperature, C-reactive protein (CRP), and white blood cell count) in children with acute illness. NTproCNP and CNP SD scores (SDSs) in the acutely ill group were significantly suppressed (P < 0.001) as compared with those of healthy children or healthy population norms. NTproCNP SDS was significantly inversely related to body temperature (r = -0.42, P < 0.01) and CRP (r = -0.56, P < 0.001). Acute inflammation in young children potently reduces CNP production, which needs to be considered when screening for growth disorders. Our data raise the possibility that the adverse effects of inflammatory cytokines on skeletal growth may be mediated in part by reduced CNP.