Rationale Heredity from mother or father may impact differently in complex diseases such as atopy. Maternal atopy is a stronger risk factor than paternal atopy for the development of atopy in the offspring. We hypothesized that mother's and father's atopy would have a differential imprinting on the cytokines and chemokines in the upper airway mucosa lining fluid of healthy neonates. Objectives We wished to study parental atopic imprinting on the cytokines and chemokines in the upper airway mucosa lining fluid of healthy neonates. Methods 18 cytokines and chemokines were quantified in nasal mucosal lining fluid in 309 neonates from the novel unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC2010) birth cohort. Measurements and Main Results Maternal, but not paternal, atopic status (asthma, hay fever and/or eczema with or without sensitization) was associated with general down-regulation of all 18 mediators assessed by principal component analysis (overall P=0.015). Conclusions Maternal atopy, but not paternal atopy, showed a strong linkage with a suppressed mucosal cytokine signature in asymptomatic neonates, suggesting imprinting by the maternal milieu in utero or perinatal life.