H7N7 low-pathogenicity avian influenza virus (H7N7-LPAIV) incursions preceded emergence of H7N7 high-pathogenicity (HP)AIV at several European layer hen outbreaks. Evidence from a UK layer H7N7-HPAIV (2008) outbreak informed in vivo modelling of sequential events, beginning with H7N7-LPAIV precursor incursion. Three groups of 17-week-old (point-of-lay) hens were inoculated with H7N7-LPAIVs, which possessed different haemagglutinin cleavage sites (CS). Groups 1 and 2 were inoculated with H7N7-LPAIVs which possessed single and di-basic cleavage sites (SBCS and DBCS) discovered at the 2008 outbreak, along with the H7N7-HPAIV’s internal genes. Group 3 was inoculated with an H7N7-LPAIV which possessed the DBCS, but different internal genes. In Groups 1-3, initial H7N7-LPAIV exposure caused limited viral shedding, restricted H7-antibody responses and no deaths by 14-days post-inoculation (dpi). H7N7-HPAIV challenge of all groups (n=8 per challenge group, including AIV-na?ve hens in Group 4) followed at 14 dpi, with 3/8 (37.5%) survival in Group 4, by 14-days post-challenge (dpc). Prior H7N7-LPAIV inoculation protected against H7N7-HPAIV challenge mortality to varying degrees (6/8-8/8 [75%-100%] survival range) by 14 dpc, when all 21 Group1-3 survivors had strongly seroconverted. Among these survivors, 20/21 (95%) shed H7N7-HP, indicating that immunity acquired during initial H7N7-LPAIV exposure did not arrest H7N7-HPAIV replication. Prior H7N7-LPAIV exposure elicited clinical protection against H7N7-HPAIV challenge, but did not prevent H7N7-HPAIV shedding, which in the field would represent a potential source for spread and further HPAIV outbreaks.