Inbreeding depression and heterosis are the two ends of phenotypic changes defined by the genome-wide homozygosity. The aim of this study was to investigate the association of genetic marker-based homozygosity estimates with 46 N-glycan features measured in human plasma. The study was based on a total of 2,341 subjects, originating from three isolated island communities in Croatia (Vis and Korcula islands) and Scotland (Orkney Islands). Inbreeding estimates were associated with an increase in tetrantennary and tetrasialylated glycans, and a decrease in digalactosylated glycans (P < 0.001). The strength of this association was proportional to the mean cohort-based inbreeding coefficient. Increase in tetraantennary glycans is known to be associated with various tumours and their association with inbreeding might be one of the mechanisms underlying the increased prevalence of tumours reported in some human isolated populations. Further studies are thus merited in order to confirm the association of inbreeding with changes in glycan profiles in other plant and animal populations, thus attempting to establish if glycosylation could indeed be involved in mediation of some phenotypic changes described in inbred and outbred organisms.