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Neonates are born with quantitative and qualitative defects in both adaptive and innate immune responses. The immune system is regulated by several mechanisms, including the signalling of inhibitory receptors. Increased expression of inhibitory receptors may result in a higher threshold for activation and suppressed function of neonatal cells. The aim of this study was to determine whether the expression of seven inhibitory receptors is increased on neonatal immune cells compared to adult immune cells. In a healthy birth cohort, we examined the expression of seven inhibitory immune receptors on neonatal neutrophils, monocytes, natural killer (NK) cells, CD4+ and CD8+ T cells. The expression of leucocyte-associated immunoglobulin (Ig)-like receptor-1 (LAIR-1), signal inhibitory receptor on leucocytes-1 (SIRL-1), CD31, signal-regulatory protein alpha (SIRPα), Siglec-9, CD200R, immune receptor expressed on myeloid cells-1 (IREM-1) and the membrane-bound ligand CD200 was studied by flow cytometry on leucocytes in cord blood (n = 14), neonatal venous blood (n = 24) and adult venous blood (n = 22). Expression of LAIR-1, CD31 and CD200 was increased consistently across all neonatal T cell subsets. Neonatal monocytes exhibited decreased expression of LAIR-1 and IREM-1 compared to adults. Furthermore, cord blood and neonatal venous blood samples contained a distinct LAIR-1-positive neutrophil population, which was not detected in adult blood. We demonstrated distinct expression of inhibitory receptors on neonatal peripheral blood immune cells in a healthy birth cohort. This is the first evidence that inhibitory receptors play a role in regulation of the neonatal immune system. Consistently increased inhibitory receptor expression on T cells may be an important mechanism in preventing the development of allergy and autoimmunity.