Background: Cell defence systems regulate homeostatic control of postprandial stress responses that are influenced by the type of food consumed and health status. Studies are required to characterise inter-individual postprandial responses to food and associations with health status. Objective: To determine postprandial effects of consuming saturated or unsaturated fats with and without antioxidant rich plant extracts and characterise corresponding cell defence system gene expression profiles in whole blood. Design: In a multiple latin square design 16 healthy volunteers consumed four food formulations (50% unsaturated or saturated fat, with or without beetroot extract 10g/100g) on separate occasions. Blood was collected at baseline and at postprandial time points 1, 2, 4, 6 and 24 hours. An in-house custom designed GenomeLab System assay measured whole blood postprandial gene expression profiles of cell defence markers, immunity, inflammation, redox, metabolism and DNA damage/repair, in response to each food formulation. Plasma markers of metabolic lipids, hormones, inflammatory cytokines, oxidative stress and DNA damage/repair were also assessed. Results: Gene expression profiles characterised postprandial immune, redox, inflammatory, metabolic and DNA damage/repair responses and revealed stratified sub-groups within the study population. Lower SIRT 1, UCP2, HO1, GSS, PTGS2, TP53, CDKN2A, PPIA and higher SOCS3 and APE1 mRNA levels stratified the study subjects. Postprandial increases in SOCS3 in sub-group 1 only and PPIA in sub-group 2 only were observed. High density lipoproteins and TNFα were associated with gene expression profiles stratifying the study subjects. Leptin, IL6 and DNA strand breaks revealed differing responses to fats used in the meal formulations. Conclusions: Gene expression profiling of human whole blood samples is a feasible approach to capturing inter-individual variation in postprandial responses in intervention studies. This approach has potential to demonstrate early changes in health status to direct prevention strategies and permit testing of dietary interventions to improve health status.