Background/aims: Food preservatives are abundant in many products in the human environment. However, little is known about the impact of many food preservatives on the immune system and the immune related genes. Hence, this study aimed to evaluate the effects of five widespread food preservatives, including butylated hydroxyanisole (BHA), potassium sorbate (PS), sodium benzoate (SB), boric acid (BA), and calcium propionate (CP), on haemato-immune functions. Method: Sixty Sprague-Dawley rats were assigned to groups orally administered water (control), BHA (0.09 mg/ kg), PS (4.5 mg/kg), SB (0.9 mg/kg), BA (0.16 mg/kg) or CP (0.18 mg/kg) for 90 consecutive days. Leukogram and erythrogram profiles were assessed. Nitric oxide and immunoglobulin levels together with phagocytic and lysozyme activities were estimated. Histologic examinations and histomorphometric analysis of splenic tissues were performed. Variations in the mRNA expression levels of tumour necrosis factor alpha (TNF-α), interferon gamma (IFNγ), interleukin (IL)-1β, IL-6, and IL-10 were assessed. Results: Anemic conditions, thrombocytopenia, leucocytopaenia simultaneous with lymphocytopaenia, monocytopenia, and esinopenia have been obvious following long term exposure to the tested food additives. Prominent exhaustion was noted in immunoglobulin and NO levels and in lysozyme and phagocytic activities. IFNγ, TNF-α, IL-1β, IL-6, and IL-10 were obviously upregulated in the groups exposed to food preservatives. Conclusion: These results confirmed that continued exposure to high levels of BHA, PS, SB, BA, and CP has haematotoxic and immunotoxic effects. Furthermore, these adverse effects are mediated by cytokine production.